CN114966056B - Kit and system for screening acute aortic dissection - Google Patents

Abstract

The invention provides a kit for screening acute aortic dissection, which comprises a reagent for detecting blood oxygen saturation, a reagent for detecting troponin T and a reagent for detecting any one or more of IL-33, SST2 and MPO; and a system for screening for acute aortic dissection. The invention can rapidly screen the acute aortic dissection through detecting a plurality of specific markers, has high specificity and sensitivity, and has important significance for early diagnosis or auxiliary diagnosis of the acute aortic dissection clinically.

Description

Screening kits and systems for acute aortic dissection

Technical Field

The invention belongs to the field of in vitro diagnostic reagents, and in particular relates to a kit and a system for screening acute aortic dissection.

Background technique

Aortic dissection (AAD) is a common cardiovascular emergency in clinical practice. Its main characteristics are that blood enters the middle layer through the aortic intima rupture on the basis of degeneration, cystic necrosis or atherosclerosis of the aortic media, resulting in pathological changes in the aorta with separated true and false lumens. AAD is usually classified into Stanford A type (the rupture is located in the ascending aorta) and Stanford B type (the rupture is located in the descending aorta or abdominal aorta) according to the location of the rupture. In recent years, with the increase in the incidence of chronic diseases such as hypertension and the deepening of population aging, the incidence of acute aortic dissection has also shown an upward trend year by year, with an annual incidence of 5-30/million. Studies have shown that about 48.6% of AAD patients die before admission to the hospital, and 30% of AAD patients die during hospitalization. For untreated patients, the risk of death within 24 hours is about 21%, the risk of death within 1 week is about 74%, and the 1-year mortality rate is as high as 93%. It is estimated that for every hour of delay in diagnosis and treatment, the risk of death in AAD patients increases by 1%-3%. On the basis of drug treatment, the early mortality rate of type A AAD patients who received surgical intervention was still 23%, and the in-hospital mortality rate of type B AAD patients was 20%. Therefore, the implementation of medical measures such as early diagnosis, early evaluation, and early treatment is the key to improving the prognosis of AAD patients. However, there are many deficiencies in the above links in the diagnosis and treatment of AAD.

The clinical diagnosis of AAD is mainly based on the patient's symptoms, physical examination, laboratory tests and imaging examinations. Since the typical symptoms of AAD are similar to those of acute chest pain (ACP) diseases such as acute myocardial infarction (AMI) and pulmonary embolism (PE), and the clinical manifestations of some AAD patients are atypical, it is easy to lead to misdiagnosis, delay patient treatment, and even give inappropriate treatment plans, increasing the risk of death. However, aortic CTA and MRA, which are the gold standards for diagnosing AAD, are not routine examination items for patients with acute chest pain, and it is difficult to perform them routinely in many primary hospitals. Therefore, to date, the diagnosis of AAD in ACP diseases is still a difficulty faced by clinicians, and there is still a lack of simple, easy-to-operate, and high-positive diagnostic methods. In addition, the early evaluation of AAD is mainly based on imaging anatomical parameters (maximum diameter of the aorta, area or volume of the false lumen, thrombosis status of the false lumen, etc.) and mechanical indicators (hemodynamic status of the true and false lumens of the aorta and the stress status of the vascular wall), but such indicators are difficult to obtain in the early stage, which is not conducive to the early risk stratification and medical decision-making of patients. Therefore, in-depth exploration of the pathogenesis and pathophysiological process of AAD and exploration of early screening and evaluation indicators will help to take intervention and treatment measures as early as possible and change the current high mortality rate of AAD.

Summary of the invention

The purpose of the present invention is to provide a kit and a system for screening acute aortic dissection.

The present invention provides use of a marker detection reagent in an acute aortic dissection screening reagent, wherein the marker detection reagent consists of a reagent for detecting blood oxygen saturation, a reagent for detecting troponin T, and a reagent for detecting any one or more of IL-33, SST2, and MPO.

Furthermore, the detection reagents of the above-mentioned markers are composed of a reagent for detecting blood oxygen saturation, a reagent for detecting troponin T, and a reagent for detecting IL-33;

Or, the marker detection reagent consists of a reagent for detecting blood oxygen saturation, a reagent for detecting troponin T, and a reagent for detecting SST2;

Alternatively, the marker detection reagent consists of a reagent for detecting blood oxygen saturation, a reagent for detecting troponin T, and a reagent for detecting MPO.

Furthermore, the above-mentioned reagent for detecting troponin T is a high-sensitivity troponin T detection reagent.

Furthermore, the above-mentioned reagent for detecting troponin T is a reagent for detecting troponin T in serum; the reagent for detecting any one or more of IL-33, SST2, and MPO is a reagent for detecting IL-33, SST2 and/or MPO in plasma.

The present invention also provides a kit for screening acute aortic dissection, which comprises a reagent for detecting blood oxygen saturation, a reagent for detecting troponin T, and a reagent for detecting any one or more of IL-33, SST2, and MPO.

Furthermore, the above-mentioned kit includes a reagent for detecting blood oxygen saturation, a reagent for detecting troponin T, and a reagent for detecting IL-33;

Or, the kit includes a reagent for detecting blood oxygen saturation, a reagent for detecting troponin T, and a reagent for detecting SST2;

Alternatively, the kit includes a reagent for detecting blood oxygen saturation, a reagent for detecting troponin T, and a reagent for detecting MPO.

Furthermore, the above-mentioned reagent for detecting troponin T is a high-sensitivity troponin T detection reagent.

The present invention also provides a system for screening acute aortic dissection, comprising an input module, a discrimination module I, a discrimination module II and an output module;

Input module: input the marker test results of patients with acute chest pain; the markers are composed of blood oxygen saturation, troponin T, and any one or more of IL-33, SST2, and MPO;

Discrimination module I: Discrimination of whether the blood oxygen saturation and the content of troponin T in serum in the marker test results meet the following conditions: blood oxygen saturation ≥ 95% and troponin T ≤ 51.3 ng/L;

Discrimination module II: Discrimination of whether the content of IL-33, SST2 and/or MPO in the marker test results meets the following requirements: IL-33 ≥ 10.96 pg/mL, SST2 ≥ 29.20 ng/mL and/or MPO ≥ 1.37 RU/mL;

Output module: outputs whether the result is acute aortic dissection;

The input module is connected to the discrimination module I, the discrimination module I is respectively connected to the discrimination module II and the output module, and the discrimination module II is connected to the output module.

Further, if the judgment result of the discrimination module I is yes, the marker detection result is input into the discrimination module II for discrimination; if the judgment result of the discrimination module I is no, the non-acute aortic dissection result is output through the output module;

If the judgment result of the discrimination module II is yes, the acute aortic dissection result is output through the output module; if the judgment result of the discrimination module II is no, the non-acute aortic dissection result is output through the output module.

Furthermore, the input module inputs the blood oxygen saturation, troponin T and IL-33 marker test results of patients with acute chest pain; the discrimination module II discriminates whether the IL-33 content in the marker test results satisfies IL-33 ≥ 10.96 pg/mL;

Or, the input module inputs the blood oxygen saturation, troponin T and SST2 marker test results of the patient with acute chest pain; the discrimination module II discriminates whether the SST2 content in the marker test results satisfies SST2 ≥ 29.20 ng/mL;

Alternatively, the input module inputs blood oxygen saturation, troponin T and MPO marker test results of patients with acute chest pain; the discrimination module II discriminates whether the MPO content in the marker test results satisfies MPO≥1.37RU/mL.

Beneficial effects of the present invention: The present invention can quickly screen for acute aortic dissection by detecting several specific markers, with high specificity and sensitivity, and is of great significance for clinical early diagnosis or auxiliary diagnosis of acute aortic dissection.

Obviously, according to the above contents of the present invention, in accordance with common technical knowledge and customary means in the art, without departing from the above basic technical ideas of the present invention, other various forms of modification, replacement or change may be made.

The above contents of the present invention are further described in detail below through specific implementation methods in the form of embodiments. However, this should not be understood as the scope of the above subject matter of the present invention being limited to the following examples. All technologies realized based on the above contents of the present invention belong to the scope of the present invention.

BRIEF DESCRIPTION OF THE DRAWINGS

Figure 1 is a schematic diagram of the marker-based acute aortic dissection screening process.

Detailed ways

The raw materials and equipment used in the present invention are all known products, which are obtained by purchasing commercially available products.

Example 1: Acute aortic dissection screening process

1. Detect IL-33, sST2 or MPO in patients with acute chest pain, and detect blood oxygen saturation and high-sensitivity troponin T (Hs-cTNT) in patients with acute chest pain.

Detection method: Enzyme-linked immunosorbent assay (ELISA) was used to quantitatively measure plasma IL-33, sST2 and serum high-sensitivity troponin T using enzyme-linked immunosorbent assay (ELISA) reagents.

The anti-MPO antibody detection kit (HBO, MY00041) was used, the magnetic microparticle chemiluminescence immunoassay was adopted, and the indirect method principle was used to detect the MPO marker through a two-step immunoassay method.

Blood oxygen saturation test: When the patient is at rest, use a fingertip photoelectric sensor and clamp the sensor on the index finger or ring finger of the left and right hands. After measuring both sides, take the average value.

2. Use the acute aortic dissection screening system to discriminate and analyze the results

The test results are input through the output module, and the discrimination module I first discriminates the blood oxygen saturation and high-sensitivity troponin T (Hs-cTNT) test results. If the blood oxygen saturation ≥ 95% and Hs-cTNT ≤ 51.3 ng/L are met at the same time, the discrimination module II is further judged. If the above conditions are not met at the same time, the result is output through the output module: "non-acute aortic dissection".

The discrimination module II determines the markers IL-33, sST2 or MPO, and there are three possible discrimination schemes:

Plan A: If IL-33 ≥ 10.96 pg/mL, the output module will output the result: "acute aortic dissection"; if IL-33 < 10.96 pg/mL, the output module will output the result: "non-acute aortic dissection".

Plan B: If sST2 ≥ 29.20 ng/mL, the output module will output the result: "acute aortic dissection"; if sST2 < 29.20 ng/mL, the output module will output the result: "non-acute aortic dissection".

Plan C: If MPO ≥ 1.37 RU/mL, the output module will output the result: "acute aortic dissection"; if MPO < 1.37 RU/mL, the output module will output the result: "non-acute aortic dissection".

The schematic diagram is shown in Figure 1.

The beneficial effects of the present invention are demonstrated by experimental examples below.

Experimental Example 1: Analysis of the screening efficacy of the present invention

1. Experimental methods

1.1 Study population

All patients with acute chest pain who met the inclusion criteria and visited the Chest Pain Center of West China Hospital, Sichuan University from 00:00 on December 1, 2019 to 23:59 on January 1, 2021 were included. The questionnaires and informed consent forms used were formulated and signed based on the "Declaration of Helsinki", and all patients and/or their agents signed the informed consent forms. The ethics of this study were reviewed and approved by the Ethics Committee of West China Hospital, Sichuan University, with the ethics approval number: 2019 Review (565).

1.2 Inclusion criteria (must be met simultaneously):

Patients who present with persistent chest and back pain as their main complaint;

Age ＞18 years old;

The initial onset of acute chest pain is less than 3 days;

1.3 Exclusion criteria (if one is met, then the case is excluded):

Patients with concurrent tumors, blood system diseases, infectious diseases, and autoimmune diseases;

Patients with a history of surgical operation within the past month;

Patients previously diagnosed with AMI, AAD, or PE;

Chest pain caused by trauma;

Patients referred after receiving treatment outside the hospital;

Patients who refused to participate in this study.

1.4 Diagnostic criteria for acute aortic dissection:

According to the definition of the "Chinese Expert Consensus on the Diagnosis and Treatment of Aortic Dissection" released in 2017, patients with acute chest pain suspected of AAD are initially screened through basic clinical data such as medical history, symptoms, signs, electrocardiogram and biomarkers, and further diagnosed with CT angiography or magnetic resonance imaging. The diagnosis is confirmed based on the observation of torn intimal sheets, intimal ruptures or false lumens.

1.5 Screening by the method of the present invention

Referring to the screening method of Example 1 (Schemes A, B, and C are performed separately), the population included in the study was screened for acute aortic dissection.

2. Experimental results

A total of 391 patients with chest pain were included in this study, with a median age of 60 (40-69) years, and 113 (28.9%) were female. According to the diagnostic criteria for acute aortic dissection, 167 (42.7%) patients were diagnosed with acute aortic dissection, and 224 patients were not diagnosed with acute aortic dissection.

The results of screening according to the screening process of Example 1 of the present invention are shown in Table 1. Based on the initial judgment based on blood oxygen saturation and high-sensitivity troponin T content, the screening process based on IL-33 (Scheme A), sST2 (Scheme B), and MPO (Scheme C) has a sensitivity of judging AAD in all chest pain patients of 0.838, 0.862, and 0.826, respectively, a specificity of 0.902, 0.938, and 0.862, and an accuracy of 0.875, 0.905, and 0.847, respectively.

Table 1 Analysis of the diagnostic efficacy of the screening process based on IL-33, sST2, and MPO for AAD

The above results indicate that the screening kit and system of the present invention have high sensitivity, specificity and accuracy in screening acute aortic dissection.

In summary, the present invention can quickly screen for acute aortic dissection by detecting several specific markers, with high specificity and sensitivity, and is of great significance for clinical early diagnosis or auxiliary diagnosis of acute aortic dissection.

Claims (3)

1. A system for screening acute aortic dissection, characterized by comprising an input module, a discrimination module I, a discrimination module II and an output module; Input module: input the marker test results of patients with acute chest pain; the markers are composed of blood oxygen saturation, troponin T, and any one or more of IL-33, SST2, and MPO; Discrimination module I: Discrimination of whether the blood oxygen saturation and troponin T content in the marker test results meet the following conditions: blood oxygen saturation ≥ 95% and troponin T ≤ 51.3 ng/L; Discrimination module II: Discrimination of whether the content of IL-33, SST2 and/or MPO in the marker test results meets the following requirements: IL-33 ≥ 10.96 pg/mL, SST2 ≥ 29.20 ng/mL and/or MPO ≥ 1.37 RU/mL; Output module: outputs whether the result is acute aortic dissection; The input module is connected to the discrimination module I, the discrimination module I is respectively connected to the discrimination module II and the output module, and the discrimination module II is connected to the output module. 2. The system as claimed in claim 1, characterized in that if the discrimination result of the discrimination module I is yes, the marker detection result is input into the discrimination module II for discrimination; if the discrimination result of the discrimination module I is no, the non-acute aortic dissection result is output through the output module; If the judgment result of the discrimination module II is yes, the acute aortic dissection result is output through the output module; if the judgment result of the discrimination module II is no, the non-acute aortic dissection result is output through the output module. 3. The system according to claim 1 is characterized in that the input module inputs the blood oxygen saturation, troponin T and IL-33 marker test results of patients with acute chest pain; the discrimination module II discriminates whether the IL-33 content in the marker test results satisfies IL-33 ≥ 10.96 pg/mL; Or, the input module inputs the blood oxygen saturation, troponin T and SST2 marker test results of the patient with acute chest pain; the discrimination module II discriminates whether the SST2 content in the marker test results satisfies SST2 ≥ 29.20 ng/mL; Alternatively, the input module inputs blood oxygen saturation, troponin T and MPO marker test results of patients with acute chest pain; the discrimination module II discriminates whether the MPO content in the marker test results satisfies MPO≥1.37RU/mL.