Type II Kounis syndrome induced by bee sting: a case report and literature review

Type II Kounis syndrome induced by bee sting: a case report and literature review | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Type II Kounis syndrome induced by bee sting: a case report and literature review Dewen Zhu, Jianqiang Meng, Yuanben Lu, Lina Chen This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5716380/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Kounis Syndrome (KS) encompasses a spectrum of clinical manifestations, including unstable angina pectoris and myocardial infarction, and is postulated to result from an exaggerated hypersensitivity reaction. This case report elucidates an instance of type II Kounis Syndrome precipitated by a bee sting, culminating in myocardial infarction—an often underrecognized and frequently misdiagnosed condition. Kounis syndrome myocardial infarction Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Kounis Syndrome (KS), also known as allergic myocardial infarction or allergic angina pectoris, is a clinical condition that has not yet received adequate recognition. This syndrome is characterized by the secretion of inflammatory cytokines through mast cell degranulation, resulting in coronary artery vasospasm, atheromatous plaque erosion, or even plaque rupture. 1 Acute myocardial ischemia is part of the clinical progression of KS, 2 which can be precipitated by various factors, including medications, insect venom, dietary allergens, environmental toxins, and underlying medical disorders. This study presents a case of KS, potentially induced by a bee sting, in which the patient exhibited the onset of angina symptoms. This case highlights the importance of increasing awareness of Kounis Syndrome, particularly among primary care physicians in emergency departments. Case prensentation A 61-year-old male presented to our emergency department with a chief complaint of experiencing breathlessness for three hours following an accidental bee sting. This incident led to progressive chest pain and the emergence of a widespread inflammatory rash. The patient's medical history is significant for smoking, excessive alcohol consumption, hypertension, coronary artery disease. His long-term pharmacological management includes oral aspirin for antiplatelet therapy and atorvastatin for lipid regulation. Upon admission, the patient's temperature was 36.7℃, heart rate 75 beats per minute, and blood pressure 121/82 mmHg, A diffuse erythematous rash was observed across the patient's body (Figure 1), and no significant abnormalities were noted upon neurological examination. Electrocardiography (ECG) demonstrated ST-segment elevation in the inferior leads (II, III, AVF) (Figure 2A), the blood tests were performed and the results showed troponin T (cTn-T) of 1.06 ng/ml and creatine kinase-muscle/brain (CK-MB) at 80.9 U/L on the second day ( Figure 3). Allergen tests revealed an IgE determination of 577.55 IU/mL (Table 1). Before admission, the patient received intravenous methylprednisolone (40 mg), a loading dose of aspirin and Tegretol in the emergency department. An urgent coronary angiography was conducted, revealing a 50% stenosis in the mid-right coronary artery (RCA)( Figure 4A), while the left anterior descending (LAD) and left circumflex (LCX, Figure 4B) arteries appeared normal. Post-operative electrocardiography (ECG) indicated that the previously elevated ST segments had returned to baseline levels (Figure 2B). During hospitalization, the patient was treated with loratadine, aspirin, clopidogrel, and atorvastatin. The patient was subsequently discharged with a full recovery. Table 1:IgE measured 577.55 IU/ml, with negative results for house dust mites and other allergens tests. Allergen Tests Results reference interval Total IGE determination 577.55 ＜ 87 I.U./ml house dust mite 0.12 ＜0.35IU/ml dust mite 0.22 ＜0.35IU/ml dog epithelial 0.12 ＜0.35IU/ml peanuts 0.05 ＜0.35IU/ml soya 0.06 ＜0.35IU/ml Milk 0.04 ＜0.35IU/ml Crab 0.07 ＜0.35IU/ml Shrimp 0.08 ＜0.35IU/ml Eggs 0.07 ＜0.35IU/ml Codfish 0.10 ＜0.35IU/ml Wheat flour 0.08 ＜0.35IU/ml Lamb 0.04 ＜0.35IU/ml Cockroaches 0.07 ＜0.35IU/ml Streptozotocin 0.04 ＜0.35IU/ml Willow 0.05 ＜0.35IU/ml Wormwood 0.08 ＜0.35IU/ml Discussion KS is an acute coronary syndrome mediated by hypersensitivity triggered by food, drugs, or environmental exposures. 3 It is characterized by "the coexistence of acute coronary syndromes associated with mast cell and platelet activation followed by allergic or anaphylactic insults," which was first described by Kounis and Zavras in 1991. Three types of KS have been identified: Type I variant refers to patients with normal or nearly normal coronary arteries, in whom KS is mainly caused by coronary artery spasm, manifested as endothelial dysfunction or microvascular angina pectoris; type II variant refers to patients with quiescent, pre-existing coronary artery stenosis, which leads to coronary plaque rupture and acute myocardial infarction when an allergic reaction occurs; and type III variant is coronary stent thrombosis, which leads to acute myocardial infarction due to acute in-stent thrombosis caused by allergic reactions. 4 Among 175 previously reported cases of Kounis Syndrome (KS), the most prevalent triggers were antibiotics (27.4%) and insect bites (23.4%). 5 Recently, a case of KS induced by the inactivated SARS-CoV-2 vaccine (CoronaVac from China) was reported in Turkey. 6 This suggests that a variety of factors can precipitate KS. A retrospective analysis was performed on a cohort of 235,420 patients admitted due to hypersensitivity and acute allergic reactions. The findings indicated an annual prevalence rate of 1.1% for Acute Coronary Syndrome (ACS), specifically identified as KS. Furthermore, significant disparities were observed in the incidence of complications between KS and non-KS patients. Notably, within the KS group, 30.4% of patients experienced cardiovascular complications, including arrhythmias. 7 Research indicates that the potential pathophysiological mechanism of Kounis syndrome involves the presence of high-affinity receptors for IgE and C5a on the cardiac mast cells. Mast cells are widely distributed throughout cardiac tissue and are predominantly found in areas with coronary plaques. Upon activation by immune or non-specific stimuli, mast cells release various vasoactive substances and inflammatory mediators such as Histamine, prostaglandin D2, leukotrienes, cytokines, thromboxane, and cysteine. These vasoactive substances can directly or indirectly induce coronary spasms. 8 The release of Histamine can result in various cardiovascular effects, including coronary vasoconstriction, decreased diastolic blood pressure, and increased intimal thickening, which may play a role in the development of coronary plaque rupture and subsequent coronary artery thrombosis as well as triggered by platelet activation and aggregation. Mast cells located in and around thrombi are believed to facilitate heparin- and tryptase-induced degradation of fibrinogen, contributing to the destabilization and maturation of thrombi. 9 Furthermore, leukotrienes exhibit potent vasoconstrictive properties, while chymase and cathepsin-D may facilitate the conversion of angiotensin I to angioten. 10 Evidence now suggests that mast cells infiltrate before plaque erosion and rupture and release their contents before coronary events. Individuals with KS present with signs and symptoms of acute coronary syndrome and evidence of a critical hypersensitivity response. The symptoms of cardiac problems may include thoracic pain, chest tightness, palpitations, dyspnea, diaphoresis, and bradycardia, skin rash, itching, hives, nausea, vomiting, wheezing, and angioedema are the signs and symptoms of an allergic reaction. Abdelghany and colleagues found that in 80% of cases, cardiac and allergic components can cause hypotensive, shock, and cardiac arrest. 5 The diagnosis of KS is based on clinical signs and symptoms, history of previous allergies, and results of laboratory tests, electrocardiogram (ECG), echocardiogram, angiogram, and magnetic resonance. Due to the lack of evidence-based medical evidence in the treatment of KS, the type I variant can be significantly improved by corticosteroids(hydrocortisone), H1 and H2 antihistamines (diphenhydramine and ranitidine), Vasodilators, such as calcium channel blockers and nitrates, which can eliminate vasospasm caused by hypersensitivity. But we must be alert that nitroglycerin can cause hypotension and tachycardia. 11 For the type II variant, an acute coronary event regimen, corticosteroids, and antihistamines should be used for the initial treatment. It should be noted that beta-blockers can increase coronary spasm due to the unopposed action of α-adrenergic receptors. Epinephrine may increase the burden of myocardial ischemia in KS, although it is the first-line treatment for allergic reactions. In severe patients, sulfite-free epinephrine is best administered by intramuscular injection because of its immediate effect and longer duration than subcutaneous injection (recommended intramuscular dose 0.2–0.5 mg). Glucagon infusion can be used in patients receiving beta-blocker therapy for the treatment of acute coronary syndromes. Individuals with KS should be wary of opioid use, such as morphine, codeine, and pethidine, as they may cause significant degranulation of mast cells and exacerbate allergic response. Paracetamol should be used with caution, as it can cause severe hypotension due to a decrease in cardiac output; Fentanyl and its derivatives are preferable because of its low level of mast cell activation. For patients with type III variants, initial treatment for acute myocardial infarction by immediate aspiration of in-stent thrombus is optimal. 12 Stent extraction is inevitable if such measures failed. With prompt treatment, good prognosis can be achieved, serious complications rarely occur, cardiogenic shock occurs in 2.3%, cardiac arrest occurs in 6.3%, and mortality is 2.9%, as reported. 13 In this case report, the patient, with a medical history of coronary artery disease, presented with symptoms indicative of an acute myocardial infarction and corresponding electrocardiographic changes following a bee sting. This was accompanied by elevated biomarkers of myocardial injury. The patient received treatment with corticosteroids and cardiovascular medications. Coronary angiography revealed no evidence of coronary occlusion, thereby confirming a diagnosis consistent with the type II variant of Kounis Syndrome. Conclusion In the context of allergic and immunological reactions, Kounis Syndrome (KS) is a frequently underdiagnosed and underestimated clinical condition that necessitates prompt decision-making and appropriate treatment. A thorough cardiac evaluation is essential, encompassing a detailed medical history, 12-lead electrocardiogram (ECG) recording, echocardiography, and potentially cardiac angiography. Declarations Acknowledgments Not applicable. Funding None. Availability of data and materials All relevant data supporting the conclusions of this article are included within the article. Ethics approval and consent to participate The study was approved by the ethics committee of Shaoxing Central Hospital, and the patient gave written consent to participate in the study. Consent for publication The patient has provided informed consent for publication of the case. Competing interests The authors declare that they have no competing interests. References Kounis NG. Kounis syndrome (allergic angina and allergic myocardial infarction): a natural paradigm? Int J Cardiol. Jun7 2006;110(1):7-14. doi:10.1016/j.ijcard.2005.08.007 Fassio F, Almerigogna F. Kounis syndrome (allergic acute coronary syndrome): different views in allergologic and cardiologic literature. Intern Emerg Med. Dec 2012;7(6):489-95. doi:10.1007/s11739-012-0754-4 Kounis NG, Patsouras N, Grapsas N, Hahalis G. Histamine induced coronary artery spasm, fish consumption and Kounis syndrome. Int J Cardiol. Aug 15 2015;193:39-41. doi:10.1016/j.ijcard.2015.05.038 Giovannini M, Koniari I, Mori F, Barni S, Novembre E, Kounis NG. Kounis syndrome: Towards a new classification. Int J Cardiol. Oct 15 2021;341:13-14. doi:10.1016/j.ijcard.2021.04.018 Kounis NG, Koniari I, Soufras GD, Patsouras N, Hahalis G. Kounis syndrome: A review article on epidemiology, diagnostic findings, management and complications of allergic acute coronary syndrome: Mastocytosis and post-mortem diagnosis. Int J Cardiol. Sep 1 2017;242:38. doi:10.1016/j.ijcard.2017.02.144 Ozdemir IH, Ozlek B, Ozen MB, Gunduz R, Bayturan O. Type 1 Kounis Syndrome Induced by Inactivated SARS-COV-2 Vaccine. J Emerg Med. Oct 2021;61(4):e71-e76. doi:10.1016/j.jemermed.2021.04.018 Abdelghany M, Subedi R, Shah S, Kozman H. Kounis syndrome: A review article on epidemiology, diagnostic findings, management and complications of allergic acute coronary syndrome. Int J Cardiol. Apr 1 2017;232:1-4. doi:10.1016/j.ijcard.2017.01.124 Kounis NG, Cervellin G, Koniari I, et al. Anaphylactic cardiovascular collapse and Kounis syndrome: systemic vasodilation or coronary vasoconstriction? Ann Transl Med. Sep 2018;6(17):332. doi:10.21037/atm.2018.09.05 Fassio F, Losappio L, Antolin-Amerigo D, et al. Kounis syndrome: A concise review with focus on management. Eur J Intern Med. May 2016;30:7-10. doi:10.1016/j.ejim.2015.12.004 Kounis NG. Coronary hypersensitivity disorder: the Kounis syndrome. Clin Ther. May 2013;35(5):563-71. doi:10.1016/j.clinthera.2013.02.022 Dogan V, Mert GO, Biteker FS, Mert KU, Biteker M. Treatment of Kounis syndrome. Int J Cardiol. Feb 15 2015;181:133-4. doi:10.1016/j.ijcard.2014.11.171 Atoui R, Mohammadi S, Shum-Tim D. Surgical extraction of occluded stents: when stenting becomes a problem. Interact Cardiovasc Thorac Surg. Oct 2009;9(4):736-8. doi:10.1510/icvts.2009.210633 Kounis NG. Kounis syndrome: an update on epidemiology, pathogenesis, diagnosis and therapeutic management. Clin Chem Lab Med. Oct 1 2016;54(10):1545-59. doi:10.1515/cclm-2016-0010 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5716380","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":395836751,"identity":"d54697f4-5293-4823-a83f-8d23dc9b189f","order_by":0,"name":"Dewen Zhu","email":"","orcid":"","institution":"Shaoxing Central Hospital","correspondingAuthor":false,"prefix":"","firstName":"Dewen","middleName":"","lastName":"Zhu","suffix":""},{"id":395836752,"identity":"4b60a9c2-162a-4a60-8933-b98b122d3ec1","order_by":1,"name":"Jianqiang Meng","email":"","orcid":"","institution":"Shaoxing Central Hospital","correspondingAuthor":false,"prefix":"","firstName":"Jianqiang","middleName":"","lastName":"Meng","suffix":""},{"id":395836753,"identity":"2c513472-dde4-43ff-a769-3c1b5a1c41af","order_by":2,"name":"Yuanben Lu","email":"","orcid":"","institution":"Shaoxing Central Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yuanben","middleName":"","lastName":"Lu","suffix":""},{"id":395836754,"identity":"7b4fbf90-146e-42ac-b92b-a8f943638455","order_by":3,"name":"Lina Chen","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAy0lEQVRIiWNgGAWjYBACPmYgwdgAYjIfOPChgggtbAgtbIkHZ5whRgsDXAuP8WHeFmK0sPMe/PBzh02e/IycDwd4Gxjk+cUOEHIYX7Jk75m0YoMzZzcckNzBYDhzdgIhLTwG0oxthxM3sPduOGB4hiHB4DZhLca/Gdv+J85v5nlwILGNOC1mQFsOJDYc72E4cJBYLZa9bcmJG84cMzjYcEaCsF/4+c8Y3/jZZpc4f0by489/Kmzk+aUJaEEHEqQpHwWjYBSMglGAHQAAucdEW44UDRUAAAAASUVORK5CYII=","orcid":"","institution":"Shaoxing Central Hospital","correspondingAuthor":true,"prefix":"","firstName":"Lina","middleName":"","lastName":"Chen","suffix":""}],"badges":[],"createdAt":"2024-12-26 13:23:08","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5716380/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5716380/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":72738942,"identity":"758af564-f63a-4628-9324-e7834764a7e6","added_by":"auto","created_at":"2025-01-01 09:21:37","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":316454,"visible":true,"origin":"","legend":"\u003cp\u003eerythematous rash on the chest and abdomen\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-5716380/v1/1b1b07032e78a468a4336e88.png"},{"id":72738941,"identity":"2f9a557f-9565-4bd4-855f-469314a03505","added_by":"auto","created_at":"2025-01-01 09:21:37","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":280263,"visible":true,"origin":"","legend":"\u003cp\u003eST segment elevation in leads II, III, AVF(A), the elevated ST-segment decreased to baseline (B)\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-5716380/v1/3f4eaf87fd93bda07dbb7f38.png"},{"id":72738943,"identity":"4c23bae7-ec36-4fa4-b7ad-660dcb50538a","added_by":"auto","created_at":"2025-01-01 09:21:37","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":47121,"visible":true,"origin":"","legend":"\u003cp\u003eSerum levels of cardiac markers showed the onset of cardiac damage, specifically dynamic changes in cTn-T (reference range:0-0.1ng/ml; right y-axis) and creatine kinase-MB (CK-MB)(reference range: 2-25 U/l; left y-axis)\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-5716380/v1/dbccfdc7e6e58187691ab278.png"},{"id":72740173,"identity":"e742db8b-1073-4d17-b2ce-43e6e5fb8455","added_by":"auto","created_at":"2025-01-01 09:29:38","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":436012,"visible":true,"origin":"","legend":"\u003cp\u003eThe angiography revealed a 50% stenosis in the mid-RCA(A), the LAD and circumflex arteries were normal(B)\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-5716380/v1/a3a2daa3aa1925018742f57b.png"},{"id":72741415,"identity":"555f6698-f3e8-4e8f-b221-f517568e37b7","added_by":"auto","created_at":"2025-01-01 09:46:26","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1624009,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5716380/v1/c619fa46-ef03-4da0-b34c-16aac238e129.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Type II Kounis syndrome induced by bee sting: a case report and literature review","fulltext":[{"header":"Introduction","content":"\u003cp\u003eKounis Syndrome (KS), also known as allergic myocardial infarction or allergic angina pectoris, is a clinical condition that has not yet received adequate recognition. This syndrome is characterized by the secretion of inflammatory cytokines through mast cell degranulation, resulting in coronary artery vasospasm, atheromatous plaque erosion, or even plaque rupture.\u003csup\u003e1\u003c/sup\u003e Acute myocardial ischemia is part of the clinical progression of KS,\u003csup\u003e2\u003c/sup\u003e which can be precipitated by various factors, including medications, insect venom, dietary allergens, environmental toxins, and underlying medical disorders. This study presents a case of KS, potentially induced by a bee sting, in which the patient exhibited the onset of angina symptoms. This case highlights the importance of increasing awareness of Kounis Syndrome, particularly among primary care physicians in emergency departments.\u003c/p\u003e"},{"header":"Case prensentation","content":"\u003cp\u003eA 61-year-old male presented to our emergency department with a chief complaint of experiencing breathlessness for three hours following an accidental bee sting. This incident led to progressive chest pain and the emergence of a widespread inflammatory rash. The patient\u0026apos;s medical history is significant for smoking, excessive alcohol consumption, hypertension, coronary artery disease. His long-term pharmacological management includes oral aspirin for antiplatelet therapy and atorvastatin for lipid regulation.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eUpon admission, the patient\u0026apos;s temperature was 36.7℃, heart rate 75 beats per minute, and blood pressure 121/82 mmHg, A diffuse erythematous rash was observed across the patient\u0026apos;s body (Figure 1), and no significant abnormalities were noted upon neurological examination. Electrocardiography (ECG) demonstrated ST-segment elevation in the inferior leads (II, III, AVF) (Figure 2A), the blood tests were performed and the results showed troponin T (cTn-T) of 1.06 ng/ml and creatine kinase-muscle/brain (CK-MB) at 80.9 U/L on the second day ( Figure 3).\u0026nbsp;Allergen tests revealed an IgE determination of 577.55 IU/mL (Table 1).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eBefore admission, the patient received intravenous methylprednisolone (40 mg), a loading dose of aspirin and Tegretol in the emergency department. An urgent coronary angiography was conducted, revealing a 50% stenosis in the mid-right coronary artery (RCA)( Figure 4A), while the left anterior descending (LAD) and left circumflex (LCX, Figure 4B) arteries appeared normal. Post-operative electrocardiography (ECG) indicated that the previously elevated ST segments had returned to baseline levels (Figure 2B). During hospitalization, the patient was treated with loratadine, aspirin, clopidogrel, and atorvastatin. The patient was subsequently discharged with a full recovery.\u003c/p\u003e\n\u003cp\u003eTable 1:IgE measured 577.55 IU/ml, with negative results for house dust mites and other allergens tests.\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" align=\"\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 176px;\"\u003e\n \u003cp\u003eAllergen Tests\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 176px;\"\u003e\n \u003cp\u003eResults\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 176px;\"\u003e\n \u003cp\u003ereference interval\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 176px;\"\u003e\n \u003cp\u003eTotal IGE determination\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 176px;\"\u003e\n \u003cp\u003e577.55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 176px;\"\u003e\n \u003cp\u003e＜ 87 I.U./ml\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 176px;\"\u003e\n \u003cp\u003ehouse dust mite\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 176px;\"\u003e\n \u003cp\u003e0.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 176px;\"\u003e\n \u003cp\u003e＜0.35IU/ml\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 176px;\"\u003e\n \u003cp\u003edust mite\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 176px;\"\u003e\n \u003cp\u003e0.22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 176px;\"\u003e\n \u003cp\u003e＜0.35IU/ml\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 176px;\"\u003e\n \u003cp\u003edog epithelial\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 176px;\"\u003e\n \u003cp\u003e0.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 176px;\"\u003e\n \u003cp\u003e＜0.35IU/ml\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 176px;\"\u003e\n \u003cp\u003epeanuts\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 176px;\"\u003e\n \u003cp\u003e0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 176px;\"\u003e\n \u003cp\u003e＜0.35IU/ml\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 176px;\"\u003e\n \u003cp\u003esoya\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 176px;\"\u003e\n \u003cp\u003e0.06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 176px;\"\u003e\n \u003cp\u003e＜0.35IU/ml\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 176px;\"\u003e\n \u003cp\u003eMilk\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 176px;\"\u003e\n \u003cp\u003e0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 176px;\"\u003e\n \u003cp\u003e＜0.35IU/ml\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 176px;\"\u003e\n \u003cp\u003eCrab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 176px;\"\u003e\n \u003cp\u003e0.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 176px;\"\u003e\n \u003cp\u003e＜0.35IU/ml\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 176px;\"\u003e\n \u003cp\u003eShrimp\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 176px;\"\u003e\n \u003cp\u003e0.08\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 176px;\"\u003e\n \u003cp\u003e＜0.35IU/ml\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 176px;\"\u003e\n \u003cp\u003eEggs\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 176px;\"\u003e\n \u003cp\u003e0.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 176px;\"\u003e\n \u003cp\u003e＜0.35IU/ml\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 176px;\"\u003e\n \u003cp\u003eCodfish\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 176px;\"\u003e\n \u003cp\u003e0.10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 176px;\"\u003e\n \u003cp\u003e＜0.35IU/ml\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 176px;\"\u003e\n \u003cp\u003eWheat flour\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 176px;\"\u003e\n \u003cp\u003e0.08\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 176px;\"\u003e\n \u003cp\u003e＜0.35IU/ml\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 176px;\"\u003e\n \u003cp\u003eLamb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 176px;\"\u003e\n \u003cp\u003e0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 176px;\"\u003e\n \u003cp\u003e＜0.35IU/ml\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 176px;\"\u003e\n \u003cp\u003eCockroaches\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 176px;\"\u003e\n \u003cp\u003e0.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 176px;\"\u003e\n \u003cp\u003e＜0.35IU/ml\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 176px;\"\u003e\n \u003cp\u003eStreptozotocin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 176px;\"\u003e\n \u003cp\u003e0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 176px;\"\u003e\n \u003cp\u003e＜0.35IU/ml\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 176px;\"\u003e\n \u003cp\u003eWillow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 176px;\"\u003e\n \u003cp\u003e0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 176px;\"\u003e\n \u003cp\u003e＜0.35IU/ml\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 176px;\"\u003e\n \u003cp\u003eWormwood\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 176px;\"\u003e\n \u003cp\u003e0.08\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 176px;\"\u003e\n \u003cp\u003e＜0.35IU/ml\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"},{"header":"Discussion","content":"\u003cp\u003eKS is an acute coronary syndrome mediated by hypersensitivity triggered by food, drugs, or environmental exposures.\u003csup\u003e3\u003c/sup\u003e It is characterized by \"the coexistence of acute coronary syndromes associated with mast cell and platelet activation followed by allergic or anaphylactic insults,\" which was first described by Kounis and Zavras in 1991.\u003c/p\u003e \u003cp\u003eThree types of KS have been identified: Type I variant refers to patients with normal or nearly normal coronary arteries, in whom KS is mainly caused by coronary artery spasm, manifested as endothelial dysfunction or microvascular angina pectoris; type II variant refers to patients with quiescent, pre-existing coronary artery stenosis, which leads to coronary plaque rupture and acute myocardial infarction when an allergic reaction occurs; and type III variant is coronary stent thrombosis, which leads to acute myocardial infarction due to acute in-stent thrombosis caused by allergic reactions.\u003csup\u003e4\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eAmong 175 previously reported cases of Kounis Syndrome (KS), the most prevalent triggers were antibiotics (27.4%) and insect bites (23.4%).\u003csup\u003e5\u003c/sup\u003e Recently, a case of KS induced by the inactivated SARS-CoV-2 vaccine (CoronaVac from China) was reported in Turkey.\u003csup\u003e6\u003c/sup\u003e This suggests that a variety of factors can precipitate KS.\u003c/p\u003e \u003cp\u003eA retrospective analysis was performed on a cohort of 235,420 patients admitted due to hypersensitivity and acute allergic reactions. The findings indicated an annual prevalence rate of 1.1% for Acute Coronary Syndrome (ACS), specifically identified as KS. Furthermore, significant disparities were observed in the incidence of complications between KS and non-KS patients. Notably, within the KS group, 30.4% of patients experienced cardiovascular complications, including arrhythmias. \u003csup\u003e7\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eResearch indicates that the potential pathophysiological mechanism of Kounis syndrome involves the presence of high-affinity receptors for IgE and C5a on the cardiac mast cells. Mast cells are widely distributed throughout cardiac tissue and are predominantly found in areas with coronary plaques. Upon activation by immune or non-specific stimuli, mast cells release various vasoactive substances and inflammatory mediators such as Histamine, prostaglandin D2, leukotrienes, cytokines, thromboxane, and cysteine. These vasoactive substances can directly or indirectly induce coronary spasms.\u003csup\u003e8\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eThe release of Histamine can result in various cardiovascular effects, including coronary vasoconstriction, decreased diastolic blood pressure, and increased intimal thickening, which may play a role in the development of coronary plaque rupture and subsequent coronary artery thrombosis as well as triggered by platelet activation and aggregation. Mast cells located in and around thrombi are believed to facilitate heparin- and tryptase-induced degradation of fibrinogen, contributing to the destabilization and maturation of thrombi.\u003csup\u003e9\u003c/sup\u003e Furthermore, leukotrienes exhibit potent vasoconstrictive properties, while chymase and cathepsin-D may facilitate the conversion of angiotensin I to angioten.\u003csup\u003e10\u003c/sup\u003e Evidence now suggests that mast cells infiltrate before plaque erosion and rupture and release their contents before coronary events.\u003c/p\u003e \u003cp\u003eIndividuals with KS present with signs and symptoms of acute coronary syndrome and evidence of a critical hypersensitivity response. The symptoms of cardiac problems may include thoracic pain, chest tightness, palpitations, dyspnea, diaphoresis, and bradycardia, skin rash, itching, hives, nausea, vomiting, wheezing, and angioedema are the signs and symptoms of an allergic reaction. Abdelghany and colleagues found that in 80% of cases, cardiac and allergic components can cause hypotensive, shock, and cardiac arrest. \u003csup\u003e5\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eThe diagnosis of KS is based on clinical signs and symptoms, history of previous allergies, and results of laboratory tests, electrocardiogram (ECG), echocardiogram, angiogram, and magnetic resonance.\u003c/p\u003e \u003cp\u003eDue to the lack of evidence-based medical evidence in the treatment of KS, the type I variant can be significantly improved by corticosteroids(hydrocortisone), H1 and H2 antihistamines (diphenhydramine and ranitidine), Vasodilators, such as calcium channel blockers and nitrates, which can eliminate vasospasm caused by hypersensitivity. But we must be alert that nitroglycerin can cause hypotension and tachycardia.\u003csup\u003e11\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eFor the type II variant, an acute coronary event regimen, corticosteroids, and antihistamines should be used for the initial treatment. It should be noted that beta-blockers can increase coronary spasm due to the unopposed action of α-adrenergic receptors. Epinephrine may increase the burden of myocardial ischemia in KS, although it is the first-line treatment for allergic reactions. In severe patients, sulfite-free epinephrine is best administered by intramuscular injection because of its immediate effect and longer duration than subcutaneous injection (recommended intramuscular dose 0.2\u0026ndash;0.5 mg). Glucagon infusion can be used in patients receiving beta-blocker therapy for the treatment of acute coronary syndromes. Individuals with KS should be wary of opioid use, such as morphine, codeine, and pethidine, as they may cause significant degranulation of mast cells and exacerbate allergic response. Paracetamol should be used with caution, as it can cause severe hypotension due to a decrease in cardiac output; Fentanyl and its derivatives are preferable because of its low level of mast cell activation.\u003c/p\u003e \u003cp\u003eFor patients with type III variants, initial treatment for acute myocardial infarction by immediate aspiration of in-stent thrombus is optimal. \u003csup\u003e12\u003c/sup\u003e Stent extraction is inevitable if such measures failed. With prompt treatment, good prognosis can be achieved, serious complications rarely occur, cardiogenic shock occurs in 2.3%, cardiac arrest occurs in 6.3%, and mortality is 2.9%, as reported.\u003csup\u003e13\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eIn this case report, the patient, with a medical history of coronary artery disease, presented with symptoms indicative of an acute myocardial infarction and corresponding electrocardiographic changes following a bee sting. This was accompanied by elevated biomarkers of myocardial injury. The patient received treatment with corticosteroids and cardiovascular medications. Coronary angiography revealed no evidence of coronary occlusion, thereby confirming a diagnosis consistent with the type II variant of Kounis Syndrome.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn the context of allergic and immunological reactions, Kounis Syndrome (KS) is a frequently underdiagnosed and underestimated clinical condition that necessitates prompt decision-making and appropriate treatment. A thorough cardiac evaluation is essential, encompassing a detailed medical history, 12-lead electrocardiogram (ECG) recording, echocardiography, and potentially cardiac angiography.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll relevant data supporting the conclusions of this article are included within the article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was approved by the ethics committee of Shaoxing Central Hospital, and the patient gave written consent to participate in the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe patient has provided informed consent for publication of the case.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eKounis NG. Kounis syndrome (allergic angina and allergic myocardial infarction): a natural paradigm? Int J Cardiol. Jun7 2006;110(1):7-14. doi:10.1016/j.ijcard.2005.08.007\u003c/li\u003e\n\u003cli\u003eFassio F, Almerigogna F. Kounis syndrome (allergic acute coronary syndrome): different views in allergologic and cardiologic literature. Intern Emerg Med. Dec 2012;7(6):489-95. doi:10.1007/s11739-012-0754-4\u003c/li\u003e\n\u003cli\u003eKounis NG, Patsouras N, Grapsas N, Hahalis G. Histamine induced coronary artery spasm, fish consumption and Kounis syndrome. Int J Cardiol. Aug 15 2015;193:39-41. doi:10.1016/j.ijcard.2015.05.038\u003c/li\u003e\n\u003cli\u003eGiovannini M, Koniari I, Mori F, Barni S, Novembre E, Kounis NG. Kounis syndrome: Towards a new classification. Int J Cardiol. Oct 15 2021;341:13-14. doi:10.1016/j.ijcard.2021.04.018\u003c/li\u003e\n\u003cli\u003eKounis NG, Koniari I, Soufras GD, Patsouras N, Hahalis G. Kounis syndrome: A review article on epidemiology, diagnostic findings, management and complications of allergic acute coronary syndrome: Mastocytosis and post-mortem diagnosis. Int J Cardiol. Sep 1 2017;242:38. doi:10.1016/j.ijcard.2017.02.144\u003c/li\u003e\n\u003cli\u003eOzdemir IH, Ozlek B, Ozen MB, Gunduz R, Bayturan O. Type 1 Kounis Syndrome Induced by Inactivated SARS-COV-2 Vaccine. J Emerg Med. Oct 2021;61(4):e71-e76. doi:10.1016/j.jemermed.2021.04.018\u003c/li\u003e\n\u003cli\u003eAbdelghany M, Subedi R, Shah S, Kozman H. Kounis syndrome: A review article on epidemiology, diagnostic findings, management and complications of allergic acute coronary syndrome. Int J Cardiol. Apr 1 2017;232:1-4. doi:10.1016/j.ijcard.2017.01.124\u003c/li\u003e\n\u003cli\u003eKounis NG, Cervellin G, Koniari I, et al. Anaphylactic cardiovascular collapse and Kounis syndrome: systemic vasodilation or coronary vasoconstriction? Ann Transl Med. Sep 2018;6(17):332. doi:10.21037/atm.2018.09.05\u003c/li\u003e\n\u003cli\u003eFassio F, Losappio L, Antolin-Amerigo D, et al. Kounis syndrome: A concise review with focus on management. Eur J Intern Med. May 2016;30:7-10. doi:10.1016/j.ejim.2015.12.004\u003c/li\u003e\n\u003cli\u003eKounis NG. Coronary hypersensitivity disorder: the Kounis syndrome. Clin Ther. May 2013;35(5):563-71. doi:10.1016/j.clinthera.2013.02.022\u003c/li\u003e\n\u003cli\u003eDogan V, Mert GO, Biteker FS, Mert KU, Biteker M. Treatment of Kounis syndrome. Int J Cardiol. Feb 15 2015;181:133-4. doi:10.1016/j.ijcard.2014.11.171\u003c/li\u003e\n\u003cli\u003eAtoui R, Mohammadi S, Shum-Tim D. Surgical extraction of occluded stents: when stenting becomes a problem. Interact Cardiovasc Thorac Surg. Oct 2009;9(4):736-8. doi:10.1510/icvts.2009.210633\u003c/li\u003e\n\u003cli\u003eKounis NG. Kounis syndrome: an update on epidemiology, pathogenesis, diagnosis and therapeutic management. Clin Chem Lab Med. Oct 1 2016;54(10):1545-59. doi:10.1515/cclm-2016-0010\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Kounis syndrome, myocardial infarction","lastPublishedDoi":"10.21203/rs.3.rs-5716380/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5716380/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eKounis Syndrome (KS) encompasses a spectrum of clinical manifestations, including unstable angina pectoris and myocardial infarction, and is postulated to result from an exaggerated hypersensitivity reaction. This case report elucidates an instance of type II Kounis Syndrome precipitated by a bee sting, culminating in myocardial infarction\u0026mdash;an often underrecognized and frequently misdiagnosed condition.\u003c/p\u003e","manuscriptTitle":"Type II Kounis syndrome induced by bee sting: a case report and literature review","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-01-01 09:21:33","doi":"10.21203/rs.3.rs-5716380/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"6dc7e857-8fed-4fc5-938f-69a46e4b306e","owner":[],"postedDate":"January 1st, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-01-01T09:38:18+00:00","versionOfRecord":[],"versionCreatedAt":"2025-01-01 09:21:33","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5716380","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5716380","identity":"rs-5716380","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}