Clinical Manifestations and Risk Factors Associated with 14 Deaths following Swarm Wasp Stings in a Chinese Tertiary Grade A General Hospital: A Retrospective Database Analysis Study 中国三级甲等综合医院 14 例蜂群蜇伤后死亡的临床表现及危险因素分析研究
Maohe Wang ^(1){ }^{1}, Mei Qin ^(1,2){ }^{1,2}, Amanda Y. Wang ^(3,4,**,t){ }^{3,4, *, t}, Jia-Wei Zhao ^(5){ }^{5}, Fei Deng ^(2){ }^{2}, Yumei Han ^(1){ }^{1} and Wei Wang ^(2,**,t){ }^{2, *, t} 王 ^(1){ }^{1} 茂和 ， 秦美 ^(1,2){ }^{1,2} ， 王 ^(3,4,**,t){ }^{3,4, *, t} 尉 ， 赵佳伟 ^(5){ }^{5} ， 邓飞 ^(2){ }^{2} ， 韩玉梅 ^(1){ }^{1} 和 王 ^(2,**,t){ }^{2, *, t} 伟1 Department of Nephrology, Suining Central Hospital, Suining 629000, China 1 遂宁市中心医院肾内科，遂宁 6290002 Renal Department and Nephrology Institute, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, China 2 电子科技大学医学院附属四川省人民医院肾病研究所，成都6100723 Renal and Metabolic Division, The George Institute for Global Health, UNSW Australia, Sydney, NSW 2052, Australia 3 澳大利亚新南威尔士大学乔治全球健康研究院肾脏与代谢科，澳大利亚新南威尔士州悉尼 20524 Department of Renal Medicine, Concord Repatriation General Hospital, Concord Clinical School, University of Sydney, Camperdown, NSW 2050, Australia 4 悉尼大学康科德临床学院康科德遣返总医院肾内科，澳大利亚新南威尔士州坎珀当 20505 Faculty of Health Sciences and Medicine, Bond University, Gold Coast, QLD 4226, Australia 5 邦德大学健康科学与医学学院，澳大利亚昆士兰州黄金海岸 4226* Correspondence: awang@georgeinstitute.org.au (A.Y.W.); wangweisz@med.uestc.edu.cn (W.W.) * 通信方式：awang@georgeinstitute.org.au （A.Y.W.）;wangweisz@med.uestc.edu.cn （W.W.）+ These authors contributed equally to the work. + 这些作者对这项工作的贡献相同。
Citation: Wang, M.; Qin, M.; Wang, A.Y.; Zhao, J.-W.; Deng, F.; Han, Y.; Wang, W. Clinical Manifestations and Risk Factors Associated with 14 Deaths following Swarm Wasp Stings in a Chinese Tertiary Grade A General Hospital: A Retrospective Database Analysis Study. J. Clin. Med. 2023, 12, 5789. https://doi.org/ 10.3390/jcm12185789 引自：Wang， M.;秦 M.;王 A.Y.;赵，JW;邓，F.;韩 Y.;Wang， W. 中国三级综合医院蜂群蜇伤后 14 例死亡的临床表现和危险因素：一项回顾性数据库分析研究。J. 克林。医学 2023， 12， 5789。https://doi.org/ 10.3390/jcm12185789
Academic Editor: Kent Doi 学术编辑：Kent Doi
Received: 21 May 2023 收稿日期： 2023-05-21
Revised: 29 August 2023 修订日期：2023 年 8 月 29 日
Accepted: 4 September 2023 录用日期： 2023-09-04
Published: 6 September 2023 发布日期：2023 年 9 月 6 日
Introduction: The objective was to evaluate the poisoning severity score (PSS) as an early prognostic predictor in patients with wasp stings and identify associated clinical characteristics and risk factors for mortality. Methods: A total of 363 patients with wasp stings at Suining Central Hospital between January 2016 and December 2018 were enrolled. Within the first 24 h of admission, the poisoning severity score (PSS) and the Chinese expert consensus on standardized diagnosis and treatment of wasp stings (CECC) were utilized for severity classification, and their correlation was examined. Patients were then divided into survival and death groups based on discharge status. Logistic regression analysis was employed to analyze factors influencing patients’ outcomes. Results: The mortality of wasp sting patients was 3.9%3.9 \%. The PSS and CECC were found to correlate for severity classification. Additionally, female gender, age, number of stings, and PSS were identified as independent risk factors for mortality in wasp sting patients. Combining these four factors yielded an AUC of 0.962 for predicting death. Conclusions: PSS aids in early severity classification of wasp stings. Female gender, age, number of stings, and PSS were independent mortality risk factors in these patients. 引言：目的是评估中毒严重程度评分 （PSS） 作为黄蜂叮咬患者的早期预后预测因子，并确定相关的临床特征和死亡危险因素。方法： 共纳入 2016年1月至 2018年12月在遂宁市中心医院就诊的 363 例黄蜂叮咬患者。在入院后最初 24 h 内，采用中毒严重程度评分 （PSS） 和中国黄蜂蜇伤规范化诊疗专家共识 （CECC） 进行严重程度分类，并检查两者的相关性。然后根据出院状态将患者分为生存组和死亡组。采用 Logistic 回归分析影响患者结局的因素。结果： 黄蜂蜇伤患者的死亡率为 3.9%3.9 \% 。发现 PSS 和 CECC 与严重程度分类相关。此外，女性性别、年龄、蜇伤次数和 PSS 被确定为黄蜂蜇伤患者死亡的独立危险因素。结合这四个因素，预测死亡的 AUC 为 0.962。结论： PSS 有助于黄蜂叮咬的早期严重程度分类。女性性别、年龄、蜇伤次数和 PSS 是这些患者的独立死亡危险因素。
The wasps belong to the order Hymenoptera [1,2]. There are more than 6000 species of wasps in the world, with more than 200 species of wasps recorded in China [3]. In Asian countries such as China and Thailand, wasps are the main species responsible for severe clinical symptoms, while carpenter bees or hornets are rarely reported to cause severe clinical symptoms [4,5]. The difference between these two families is easy to recognize. For example, bee or hornet stings usually stay on the victim’s skin, while wasp stings do not [2]. Wasps attack humans in self-defense, and when threatened, they emit warning calls or release a special odor that attracts other wasps to attack. Their venom can cause severe health problems in human beings [6,7]. 黄蜂属于膜翅目 [1,2]。世界上有 6000 多种黄蜂，其中中国记录的黄蜂有 200 多种 [3]。在中国和泰国等亚洲国家，黄蜂是导致严重临床症状的主要物种，而木蜂或大黄蜂很少报道引起严重临床症状[4,5]。这两个家族之间的区别很容易识别。例如，蜜蜂或大黄蜂蜇伤通常会留在受害者的皮肤上，而黄蜂蜇伤则不会[2]。黄蜂出于自卫而攻击人类，当受到威胁时，它们会发出警告或释放特殊气味，吸引其他黄蜂攻击。它们的毒液可导致人类出现严重的健康问题[6,7]。
China is a large agricultural country. With developments in returning farmland to forests in rural areas, vegetation is becoming more and more abundant, providing a suitable habitat for wasps; thus, the incidence of wasp stings is increasing, bringing a serious burden 中国是一个农业大国。随着农村地区退耕还林的发展，植被越来越丰富，为黄蜂提供了合适的栖息地;因此，黄蜂叮咬的发生率正在增加，带来了严重的负担
to people’s public health and social economy [5,8]. One or two stings usually result in a mild local reaction, including redness, pain, swelling, rash, or anaphylaxis. A swarm attack can lead to serious systemic toxicity, such as rhabdomyolysis, hemolysis, ARDS (acute respiratory distress syndrome), AKI (acute kidney injury) and death [9-11]. The mortality after wasp stings ranged from 5.1 to 21%21 \% [5]. It is particularly important to classify the severity at an early stage and to carry out the corresponding treatment [12,13]. The severity of wasp stings is related to the species and the number of stings; however, the severity of wasp stings and its clinical course may not be shown immediately at presentation. In China, most wasp stings occur in rural areas [12]. Primary medical institutions lack adequate knowledge of the severity of wasp stings, which may delay appropriate treatment decisions for these patients. Therefore, a simple and easy-to-understand tool combining clinical and biochemical parameters may assist physicians in instituting appropriate management and predicting outcomes. Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation (APACHEII) scores have been used to classify the severity of wasp sting patients [9,10,14]. However, as these systems were designed to identify patients at risk of deterioration in the ICU, they were unable to identify patients with severe wasp stings at an early stage. In the “Chinese expert consensus on standardized diagnosis and treatment of wasp stings (CECC)”, published in 2018, a guide to classifying the severity of wasp stings was described, but it has not been widely used [12]. In Europe, the poisoning severity score (PSS) was used to assess the severity of poisoning patients (including environmental toxins) [15]. Stays for observation, hospitalization, admission to ICU or general ward and nursing grade were decided according to the assessment results [16]. However, to the author’s knowledge, no previous study has specifically addressed the use of PSS to assess the severity of wasp stings in patients. Therefore, we conducted this study to evaluate the usefulness of PSS as an early prognostic indicator for short-term outcomes in a cohort of 363 patients with wasp stings at Suining Central Hospital from January 2016 to December 2018. Additionally, our study also aimed to explore the clinical characteristics and risk factors associated with mortality. Identifying these factors could play a vital role in effectively identifying high-risk patients and optimizing their management. Ultimately, this knowledge has the potential to contribute to reducing the fatality rate associated with wasp stings. 对人们的公共卫生和社会经济的影响 [5,8]。一两次蜇伤通常会导致轻微的局部反应，包括发红、疼痛、肿胀、皮疹或过敏反应。集群攻击可导致严重的全身毒性反应，如横纹肌溶解、溶血、ARDS（急性呼吸窘迫综合征）、AKI（急性肾损伤）和死亡[9-11]。黄蜂叮咬后的死亡率从 5.1 到 21%21 \% [5] 不等。在早期对严重程度进行分类并进行相应的治疗尤为重要[12,13]。黄蜂蜇伤的严重程度与物种和蜇伤次数有关;然而，WASP 蜇伤的严重程度及其临床病程可能不会在就诊时立即显示。在中国，大多数黄蜂叮咬发生在农村地区 [12]。初级医疗机构对黄蜂叮咬的严重程度缺乏足够的了解，这可能会延迟为这些患者做出适当的治疗决策。因此，一种结合了临床和生化参数的简单易懂的工具可以帮助医生制定适当的管理和预测结果。序贯器官衰竭评估 （SOFA） 和急性生理学和慢性健康评估 （APACHEII） 评分已被用于对黄蜂叮咬患者的严重程度进行分类 [9,10,14]。然而，由于这些系统旨在识别 ICU 中有恶化风险的患者，因此它们无法在早期识别严重黄蜂叮咬的患者。在 2018 年出版的《黄蜂蜇伤规范化诊治中国专家共识 （CECC）》中，描述了黄蜂蜇伤严重程度分类指南，但尚未得到广泛应用 [12]。 在欧洲，PSS 用于评估中毒患者（包括环境毒素）的严重程度 [15]。根据评估结果决定观察、住院、入住 ICU 或普通病房和护理等级的住院时间 [16]。然而，据作者所知，之前没有研究专门讨论使用 PSS 来评估患者黄蜂蜇伤的严重程度。因此，我们进行了这项研究，以评估 PSS 作为 2016 年 1 月至 2018 年 12 月在遂宁市中心医院 363 例黄蜂叮咬患者队列中短期结局的早期预后指标的有用性。此外，我们的研究还旨在探讨与死亡率相关的临床特征和风险因素。识别这些因素可能在有效识别高危患者和优化其管理方面发挥至关重要的作用。最终，这些知识有可能有助于降低与黄蜂叮咬相关的死亡率。
2. Materials and Methods 2. 材料和方法
2.1. Ethics Statement 2.1. 道德声明
This retrospective study was approved by the IRB (Institutional Review Board) of Suining Central Hospital (Approval No. LLSNCH20200022). Considering the nature of the retrospective study design to review the medical records of patients who completed the treatment, IRB waived the requirement to obtain informed consent. All procedures that involved human participants were conducted in accordance with the ethical standards of the institutional and/or national research committees and compliance with the 1964 Declaration of Helsinki and its later amendments or other comparable ethical standards. 该回顾性研究已获得遂宁市中心医院 IRB（机构审查委员会）的批准（批准号。LLSNCH20200022）。考虑到回顾性研究设计的性质，以审查完成治疗的患者的病历，IRB 放弃了获得知情同意的要求。所有涉及人类参与者的程序均按照机构和/或国家研究委员会的道德标准进行，并遵守 1964 年赫尔辛基宣言及其后来的修正案或其他类似的道德标准。
2.2. Research Subjects 2.2. 研究对象
Due to the implementation of the home quarantine policy in response to the COVID-19 pandemic, there has been a notable decrease in the number of individuals seeking medical attention for wasp stings. To accurately represent the pre-COVID-19 circumstances, our study focused on data collected prior to the implementation of this policy. Specifically, we conducted a retrospective study involving patients with wasp stings who sought treatment at the nephrology department and ICU of Suining Central Hospital in Sichuan Province, China, from January 2016 to December 2018. Suining Central Hospital, located in the interior regions of Sichuan Province, is the sole tertiary grade A general hospital in this area. With an annual intake of over 94,000 hospitalized patients, the hospital typically treats more than 100 cases of wasp stings each year. 由于为应对 COVID-19 大流行而实施的居家隔离政策，因黄蜂叮蛰而寻求医疗护理的人数显著减少。为了准确反映 COVID-19 之前的情况，我们的研究侧重于在实施该政策之前收集的数据。具体来说，我们进行了一项回顾性研究，涉及 2016 年 1 月至 2018 年 12 月在中国四川省遂宁市中心医院肾内科和 ICU 寻求治疗的黄蜂叮咬患者。遂宁市中心医院位于四川省内陆地区，是该地区唯一的三级甲等综合医院。该医院每年接收超过 94,000 名住院患者，通常每年治疗 100 多例黄蜂叮咬病例。
The inclusion criteria were: (1) patients with a definite diagnosis of wasp stings; (2) age >= 14\geq 14 years old; (3) the clinical data were complete. The exclusion criteria were as follows: (1) age < 14 years; (2) re-hospitalized patients with wasp stings; (3) wasp sting patients who died before admission; (4) asymptomatic patients; (5) patients who refuse to be admitted to the hospital; (6) patients dead on arrival. We categorized them into survival group (n=349)(n=349) and death group (n=14)(n=14) according to the state of discharge. 纳入标准是： （1） 明确诊断为黄蜂蜇伤的患者;（2） 年龄 >= 14\geq 14 岁;（3） 临床资料完整。排除标准如下： （1） 年龄 < 14 岁;（2） 黄蜂叮咬再住院患者;（3） 入院前死亡的黄蜂叮咬患者;（4） 无症状患者;（5） 拒绝入院的患者;（6） 到达时死亡的患者。我们根据出院状态将他们分为生存组 (n=349)(n=349) 和死亡组 (n=14)(n=14) 。
2.3. Definitions 2.3. 定义
Hypotension was defined as a systolic blood pressure below 90 mmHg or a diastolic blood pressure below 60 mmHg . Acute kidney injury (AKI) was defined based on the following criteria: a rapid increase in serum creatinine levels, indicated by an increase of >= 0.3mg//dL(26.5 mumol//L)\geq 0.3 \mathrm{mg} / \mathrm{dL}(26.5 \mu \mathrm{~mol} / \mathrm{L}) within 48 h compared to baseline, or an increase in creatinine level to 1.5 times or more of the baseline value. Decreased urine output was defined as urine output less than 0.5mL//kg//h0.5 \mathrm{~mL} / \mathrm{kg} / \mathrm{h} for at least 6 consecutive hours during the oliguric phase [17]. Rhabdomyolysis was defined as serum creatine kinase (CK) level > 1000U//L1000 \mathrm{U} / \mathrm{L} or at least 5 times the upper limit of normal [18]. Coagulation abnormalities were determined by the following criteria: activated partial thromboplastin time (aPTT) exceeding the upper limit of normal or prothrombin time (PT) exceeding the upper limit of normal. Liver damage was assessed by elevated levels of alanine aminotransferase (ALT) or aspartate aminotransferase (AST), exceedingly the upper limit of normal values. Hemolysis can be described concisely as follows: the presence of clinical signs and symptoms consistent with hemolysis, such as anemia, jaundice, and/or dark urine. Laboratory evidence of red blood cell destruction, including increased levels of indirect bilirubin and lactate dehydrogenase (LDH) [19]. 低血压定义为收缩压低于 90 mmHg 或舒张压低于 60 mmHg。急性肾损伤 （AKI） 根据以下标准定义： 血清肌酐水平快速升高，表现 >= 0.3mg//dL(26.5 mumol//L)\geq 0.3 \mathrm{mg} / \mathrm{dL}(26.5 \mu \mathrm{~mol} / \mathrm{L}) 为与基线相比在 48 小时内增加，或肌酐水平增加至基线值的 1.5 倍或更多。尿量减少定义为在少尿期尿量少于 0.5mL//kg//h0.5 \mathrm{~mL} / \mathrm{kg} / \mathrm{h} 至少连续 6 小时 [17]。横纹肌溶解症定义为血清肌酸激酶 （CK） 水平> 1000U//L1000 \mathrm{U} / \mathrm{L} 或至少是正常上限的 5 倍 [18]。凝血异常由以下标准确定： 活化部分凝血活酶时间 （aPTT） 超过正常上限或凝血酶原时间 （PT） 超过正常上限。通过丙氨酸氨基转移酶 （ALT） 或天冬氨酸氨基转移酶 （AST） 水平升高来评估肝损伤，超过正常值的上限。溶血可以简明扼要地描述如下：存在与溶血一致的临床体征和症状，例如贫血、黄疸和/或深色尿。红细胞破坏的实验室证据，包括间接胆红素和乳酸脱氢酶（LDH）水平升高[19]。
2.4. Clinical Data Collection 2.4. 临床数据收集
Following the approval of the IRB application, we collected the patients’ data from medical records. We collected information on the patients’ demographics (age, gender), the time interval between sting and admission (admission time), number of stings, signs and symptoms (allergic rash, hypotension, macroscopic hematuria, and oliguria or anuria), severe complications (rhabdomyolysis, acute kidney injury (AKI), coagulation disorders, hemolysis, liver dysfunction, acute respiratory distress syndrome (ARDS) and multiple organ dysfunction syndrome (MODS)), inpatient days, and short-term outcomes (death or survival). 在 IRB 申请获得批准后，我们从病历中收集了患者的数据。我们收集了患者的人口统计学信息（年龄、性别）、蜇伤和入院之间的时间间隔（入院时间）、蜇伤次数、体征和症状（过敏性皮疹、低血压、肉眼血尿、少尿或无尿）、严重并发症（横纹肌溶解、急性肾损伤 （AKI）、凝血障碍、溶血、肝功能障碍、急性呼吸窘迫综合征 （ARDS） 和多器官功能障碍综合征 （MODS））、 住院天数和短期结果（死亡或生存）。
We recorded laboratory data on admission, including white blood cells (WBC), activated partial thromboplastin time (APTT), prothrombin time (PT), alanine aminotransferase (ALT), aspartate aminotransferase (AST), indirect bilirubin (I-BIL), creatine kinase (CK), lactate dehydrogenase (LDH), and serum creatinine (SCr). 我们记录了入院的实验室资料，包括白细胞 （WBC） 、活化部分凝血活酶时间 （APTT） 、凝血酶原时间 （PT） 、丙氨酸氨基转移酶 （ALT） 、天冬氨酸氨基转移酶 （AST）、间接胆红素 （I-BIL） 、肌酸激酶 （CK） 、乳酸脱氢酶 （LDH） 和血清肌酐 （SCr）。
2.5. At Admission, PSS and CECC Were Used as the Criterion for Severity Classification Respectively 2.5. 入院时，PSS 和 CECC 分别用作严重程度分类的标准
The classification of patients using the PSS and CECC was done retrospectively upon admission. The symptoms and signs of the patients were obtained from their medical records, and trained professionals performed the evaluation using the PSS and CECC criteria. 使用 PSS 和 CECC 对患者进行入院时回顾性分类。患者的症状和体征是从他们的病历中获得的，训练有素的专业人员使用 PSS 和 CECC 标准进行了评估。
The aim of the PSS is to provide a standardized assessment of the severity of poisoning based on clinical manifestations for research and clinical purposes. It is important to note that the PSS grading system solely considers the observed clinical symptoms and signs and does not take into account factors such as the amount ingested or serum concentrations of the toxic agent. The poisoning severity score (PSS) classifies patients into different severity levels based on observed clinical symptoms and signs related to poisoning. The classification is as follows: (0) none: no symptoms or signs related to poisoning; (1) minor: mild, transient, and spontaneously resolving symptoms; (2) moderate: pronounced or prolonged symptoms; (3) severe: severe or life-threatening symptoms; and (4) fatal poisoning: death. Patients only needed to meet one or more of the criteria to be classified accordingly [20]. PSS 的目的是根据临床表现为研究和临床目的提供中毒严重程度的标准化评估。需要注意的是，PSS 分级系统仅考虑观察到的临床症状和体征，而不考虑摄入量或毒性物质的血清浓度等因素。中毒严重程度评分 （PSS） 根据观察到的与中毒相关的临床症状和体征将患者分为不同的严重程度。分类如下： （0） 无：无中毒相关症状或体征;（1） 轻微：轻度、短暂且自发消退的症状;（2） 中度：明显或持续的症状;（3） 严重：严重或危及生命的症状;（4） 致命中毒：死亡。患者只需满足一项或多项标准即可进行相应分类 [20]。
