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Adaptive platform trials in critical care 重症监护中的适应性平台试验
Pub Date : 2024-05-29 DOI: 10.1016/j.jointm.2024.04.002
Muralie Vignarajah , Bram Rochwerg
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引用次数: 0
Comparative study on the incidence of non-COVID-19 viral pneumonia before and after the COVID-19 pandemic: A retrospective analysis based on respiratory non-COVID viral nucleic acid results COVID-19 大流行前后非 COVID-19 病毒性肺炎发病率的比较研究:基于呼吸道非 COVID 病毒核酸结果的回顾性分析
Pub Date : 2024-04-23 DOI: 10.1016/j.jointm.2024.02.005

Background

The impact of the coronavirus disease 2019 (COVID-19) pandemic on the etiology of non-COVID-19 viral pneumonia remains to be identified. We investigated the evolution of non-COVID-19 viral pneumonia in hospitalized patients before and after the COVID-19 pandemic.

Methods

This is a single-center retrospective study. Patients who came to West China Hospital of Sichuan University diagnosed with non-COVID-19 viral pneumonia from January 1, 2016 to December 31, 2021, were included and divided into pre- and post-COVID-19 groups according to the date of the COVID-19 outbreak in China. The results of 13 viral nucleic acid tests were compared between the two groups.

Results

A total of 5937 patients (3954 in the pre-COVID-19 group and 1983 in the post-COVID-19 group) were analyzed. Compared with the pre-COVID-19 group, the proportion of patients tested for respiratory non-COVID-19 viral nucleic acid was significantly increased in the post-COVID-19 group (14.78% vs. 22.79%, P <0.05). However, the non-COVID-19 virus-positive rates decreased from 37.9% to 14.6% after the COVID-19 outbreak (P < 0.001). Notably, non-COVID-19 viral pneumonia caused by the influenza A virus H1N1 (InfAH1N1) (2009) dropped to 0% after the pandemic. The top three viruses were InfAH1N1 (2009) (13.9%), human rhinovirus (7.4%), and human adenovirus (3.4%) in the pre-COVID-19 group, and human rhinovirus (3.8%), human respiratory syncytial virus (2.0%), human parainfluenza virus (1.1%) and InfAH3N2 (1.1%) in the post-COVID-19 group.

Conclusions

The proportion of non-COVID-19 viral pneumonia decreased significantly after the COVID-19 outbreak, among which InfAH1N1 (2009) pneumonia decreased the most dramatically.

背景2019年冠状病毒病(COVID-19)大流行对非COVID-19病毒性肺炎病因的影响仍有待确定。我们调查了COVID-19大流行前后住院患者非COVID-19病毒性肺炎的演变情况。纳入2016年1月1日至2021年12月31日到四川大学华西医院就诊的非COVID-19病毒性肺炎患者,并根据COVID-19在中国爆发的日期分为COVID-19之前组和COVID-19之后组。结果 共分析了 5937 例患者(COVID-19 之前组 3954 例,COVID-19 之后组 1983 例)。与 COVID-19 前组相比,COVID-19 后组中接受呼吸道非 COVID-19 病毒核酸检测的患者比例显著增加(14.78% 对 22.79%,P <0.05)。然而,COVID-19 爆发后,非 COVID-19 病毒阳性率从 37.9% 降至 14.6%(P <0.001)。值得注意的是,甲型 H1N1 流感病毒(InfAH1N1)(2009 年)引起的非 COVID-19 病毒性肺炎在大流行后降至 0%。在 COVID-19 之前的组别中,排在前三位的病毒分别是 InfAH1N1(2009)(13.9%)、人类鼻病毒(7.4%)和人类腺病毒(3.4%),以及人类鼻病毒(3.8%)、人类呼吸道合胞病毒(2.0%)、人类副流感病毒(1.结论 COVID-19 爆发后,非 COVID-19 病毒性肺炎的比例显著下降,其中 InfAH1N1(2009 年)肺炎的下降幅度最大。
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引用次数: 0
Severe respiratory syncytial virus disease 严重呼吸道合胞病毒病
Pub Date : 2024-04-20 DOI: 10.1016/j.jointm.2024.03.001

The burden of respiratory syncytial virus (RSV) disease is widely recognized. Main risk factors for severe disease, such as extreme ages, chronic cardiopulmonary conditions, and immunosuppression, typically coincide with poorer outcomes. While the majority of RSV hospitalizations involve healthy children, a higher proportion of hospitalized adults with underlying conditions need intensive care. Presently, treatment primarily consists of supportive measures. RSV-induced wheezing should be distinguished from respiratory tract thickening, without response to bronchodilators. Obstructive RSV disease frequently overlaps with viral pneumonia. Non-invasive mechanical ventilation and high-flow oxygen therapy represented significant advancements in the management of severe RSV disease in children and may also hold considerable importance in specific phenotypes of RSV disease in adults. Most severe infections manifest with refractory hypoxemia necessitating more advanced ventilatory support and/or extracorporeal membrane oxygenation therapy. Although bacterial co-infection rates are low, they have been associated with worse outcomes. Antibiotic prescription rates are high. Accurately diagnosing bacterial co-infections remains a challenge. Current evidence and antibiotic stewardship policies advise against indiscriminate antibiotic usage, even in severe cases. The role of currently developing antiviral therapies in severe RSV disease will be elucidated in the coming years, contingent upon the success of new vaccines and immune passive strategies involving nirsevimab.

呼吸道合胞病毒(RSV)疾病造成的负担已得到广泛认可。严重疾病的主要风险因素,如极端年龄、慢性心肺疾病和免疫抑制,通常与较差的治疗效果相吻合。虽然大多数住院的 RSV 患者都是健康儿童,但有更高比例的住院成年人因潜在疾病而需要重症监护。目前,治疗主要包括支持性措施。应将 RSV 引起的喘息与呼吸道增厚(对支气管扩张剂无反应)区分开来。阻塞性 RSV 疾病经常与病毒性肺炎重叠。无创机械通气和高流量供氧疗法是治疗儿童严重 RSV 疾病的重大进展,对于成人 RSV 疾病的特定表型可能也相当重要。大多数严重感染表现为难治性低氧血症,需要更先进的通气支持和/或体外膜氧合疗法。虽然细菌合并感染率较低,但却与较差的预后有关。抗生素处方率很高。准确诊断细菌合并感染仍是一项挑战。目前的证据和抗生素管理政策建议不要滥用抗生素,即使是在严重病例中。未来几年,新疫苗和涉及 nirsevimab 的免疫被动策略能否取得成功,将决定目前开发的抗病毒疗法在重症 RSV 疾病中的作用。
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引用次数: 0
How much tidal volume is sufficiently low to be called “protective lung ventilation” 多少潮气量才足以称为 "保护性肺通气"
Pub Date : 2024-04-17 DOI: 10.1016/j.jointm.2024.03.002

Ultra-low tidal volume (ULT) is an appealing alternative for severe acute respiratory distress syndrome (ARDS) patients with the aim to alleviate excess lung stress and strain. A recent article showed that ULT without extracorporeal carbon dioxide removal did not improve prognosis in moderate-to-severe coronavirus disease 2019-related ARDS patients. However, several reasons should be considered before drawing the definite conclusion about the ULT strategy in severe ARDS.

对于严重急性呼吸窘迫综合征(ARDS)患者来说,超低潮气量(ULT)是一种很有吸引力的选择,其目的是减轻肺部过多的压力和负荷。最近的一篇文章显示,不进行体外二氧化碳清除的超低潮气量治疗并不能改善中重度冠状病毒病2019相关ARDS患者的预后。然而,在对重度ARDS患者的超低温治疗策略得出明确结论之前,应考虑几个原因。
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引用次数: 0
Severe aspiration pneumonia in the elderly 老年人严重吸入性肺炎
Pub Date : 2024-04-10 DOI: 10.1016/j.jointm.2023.12.009
Sebastian Ocrospoma , Marcos I. Restrepo

The global population is aging at an unprecedented rate, resulting in a growing and vulnerable elderly population in need of efficient comprehensive healthcare services that include long-term care and skilled nursing facilities. In this context, severe aspiration pneumonia, a condition that carries substantial morbidity, mortality, and financial burden, especially among elderly patients requiring admission to the intensive care unit, has attracted greater concern. Aspiration pneumonia is defined as a pulmonary infection related to aspiration or dysphagia in etiology. Prior episodes of coughing on food or liquid intake, a history of relevant underlying conditions, abnormalities on videofluoroscopy or water swallowing, and gravity-dependent shadow distribution on chest imaging are among the clues that suggest aspiration. Patients with aspiration pneumonia tend to be elderly, frail, and suffering from more comorbidities than those without this condition. Here, we comprehensively address the epidemiology, clinical characteristics, diagnosis, treatment, prevention, and prognosis of severe aspiration community-acquired pneumonia in the elderly to optimize care of this high-risk demographic, enhance outcomes, and minimize the healthcare costs associated with this illness. Emphasizing preventive measures and effective management strategies is vital in ensuring the well-being of our aging population.

全球人口正以前所未有的速度步入老龄化社会,这导致老年人口不断增加,且易受伤害,他们需要高效、全面的医疗保健服务,包括长期护理和专业护理设施。在这种情况下,重症吸入性肺炎这种会带来大量发病率、死亡率和经济负担的疾病,尤其是需要入住重症监护病房的老年患者,引起了人们更多的关注。吸入性肺炎是指病因与吸入或吞咽困难有关的肺部感染。吸入食物或液体时曾出现咳嗽、相关基础疾病史、视频荧光镜检查或吞咽水时出现异常、胸部影像学检查出现重力依赖性阴影分布等都是吸入性肺炎的线索。与非吸入性肺炎患者相比,吸入性肺炎患者往往年老体弱,合并症较多。在此,我们将全面阐述老年人重症吸入性社区获得性肺炎的流行病学、临床特征、诊断、治疗、预防和预后,以优化对这一高风险人群的护理,提高疗效,并最大限度地降低与该疾病相关的医疗成本。强调预防措施和有效的管理策略对于确保老龄人口的福祉至关重要。
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引用次数: 0
Pathophysiological dynamics in the contact, coagulation, and complement systems during sepsis: Potential targets for nafamostat mesilate 败血症期间接触、凝血和补体系统的病理生理动态:甲磺酸萘莫司他的潜在靶点
Pub Date : 2024-04-10 DOI: 10.1016/j.jointm.2024.02.003

Sepsis is a life-threatening syndrome resulting from a dysregulated host response to infection. It is the primary cause of death in the intensive care unit, posing a substantial challenge to human health and medical resource allocation. The pathogenesis and pathophysiology of sepsis are complex. During its onset, pro-inflammatory and anti-inflammatory mechanisms engage in intricate interactions, possibly leading to hyperinflammation, immunosuppression, and long-term immune disease. Of all critical outcomes, hyperinflammation is the main cause of early death among patients with sepsis. Therefore, early suppression of hyperinflammation may improve the prognosis of these patients. Nafamostat mesilate is a serine protease inhibitor, which can inhibit the activation of the complement system, coagulation system, and contact system. In this review, we discuss the pathophysiological changes occurring in these systems during sepsis, and describe the possible targets of the serine protease inhibitor nafamostat mesilate in the treatment of this condition.

败血症是由于宿主对感染的反应失调而导致的危及生命的综合征。它是重症监护病房的主要死亡原因,对人类健康和医疗资源分配构成了巨大挑战。败血症的发病机制和病理生理学十分复杂。在发病过程中,促炎和抗炎机制会发生错综复杂的相互作用,可能导致炎症过度、免疫抑制和长期免疫疾病。在所有严重后果中,高炎症是导致败血症患者早期死亡的主要原因。因此,尽早抑制高炎症可改善这些患者的预后。甲磺酸萘莫司他是一种丝氨酸蛋白酶抑制剂,可抑制补体系统、凝血系统和接触系统的激活。在这篇综述中,我们讨论了败血症期间这些系统发生的病理生理学变化,并描述了丝氨酸蛋白酶抑制剂甲磺酸纳伐司他在治疗这种病症中可能的靶点。
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引用次数: 0
Relevance of plasma lipoproteins and small metabolites in assessment of nutritional status among patients with severe injuries 血浆脂蛋白和小代谢物在评估重伤患者营养状况中的相关性
Pub Date : 2024-04-10 DOI: 10.1016/j.jointm.2024.02.004

Background

This study aimed to identify plasma lipoproteins and small metabolites associated with high risk of malnutrition during intensive care unit (ICU) stay in patients with severe injuries.

Methods

This observational prospective exploratory study was conducted at two level-1 trauma centers in the Netherlands. Adult patients (aged ≥18 years) who were admitted to the ICU for more than 48 h between July 2018 and April 2022 owing to severe injuries (polytrauma, as defined by Injury Severity Scores of ≥16) caused by blunt trauma were eligible for inclusion. Partial least squares discriminant analysis was used to analyze the relationship of 112 lipoprotein-related components and 23 small metabolites with the risk of malnutrition (modified Nutrition Risk in Critically Ill score). Malnutrition was diagnosed based on Subjective Global Assessment scores. The relationship of lipoprotein properties and small metabolite concentrations with malnutrition (during ICU admission) was evaluated using mixed effects logistic regression.

Results

Overall, 51 patients were included. Lower (very) low-density lipoprotein ([V]LDL) (free) cholesterol and phospholipid levels, low particle number, and higher levels of LDL triglycerides were associated with a higher risk of malnutrition (variable importance in projection [VIP] value >1.5). Low levels of most (V)LDL and intermediate-density lipoprotein subfractions and high levels of high-density lipoprotein Apo-A1 were associated with the diagnosis of malnutrition (VIP value >1.5). Increased levels of dimethyl sulfone, trimethylamine N-oxide, creatinine, N, N-dimethylglycine, and pyruvic acid and decreased levels of creatine, methionine, and acetoacetic acid were also indicative of malnutrition (VIP value >1.5). Overall, 14 lipoproteins and 1 small metabolite were significantly associated with a high risk of malnutrition during ICU admission (P <0.05); however, the association did not persist after correcting the false discovery rate (P=0.35 for all).

Conclusion

Increased triglyceride in several lipoprotein subfractions and decreased levels of other lipoprotein subfraction lipids and several small metabolites (involved in the homocysteine cycle, ketone body formation, and muscle metabolism) may be indicative of malnutrition risk. Following validation in larger cohorts, these indicators may guide institution of preventive nutritional measures in patients admitted to the ICU with severe injuries.

背景本研究旨在确定与重症监护室(ICU)重伤患者住院期间营养不良高风险相关的血浆脂蛋白和小代谢物。方法本观察性前瞻性探索研究在荷兰的两家一级创伤中心进行。2018年7月至2022年4月期间,因钝性创伤导致的严重损伤(多发性创伤,由损伤严重程度评分≥16分定义)而入住重症监护室超过48小时的成年患者(年龄≥18岁)符合纳入条件。采用偏最小二乘法判别分析法分析了112种脂蛋白相关成分和23种小代谢物与营养不良风险的关系(修改后的重症患者营养风险评分)。营养不良的诊断依据是主观全面评估评分。采用混合效应逻辑回归法评估了脂蛋白特性和小代谢物浓度与营养不良(入ICU期间)的关系。较低的(极)低密度脂蛋白([V]LDL)(游离)胆固醇和磷脂水平、较低的颗粒数和较高的低密度脂蛋白甘油三酯水平与较高的营养不良风险有关(预测中的变量重要性[VIP]值为1.5)。大多数(V)低密度脂蛋白和中密度脂蛋白亚组分的低水平以及高密度脂蛋白载脂蛋白-A1的高水平与营养不良的诊断有关(VIP值为1.5)。二甲基砜、三甲胺 N-氧化物、肌酐、N,N-二甲基甘氨酸和丙酮酸水平升高以及肌酸、蛋氨酸和乙酰乙酸水平降低也表明存在营养不良(VIP 值为 1.5)。总之,14 种脂蛋白和 1 种小代谢物与入住 ICU 期间营养不良的高风险显著相关(P <0.05);然而,在校正误发现率后,这种相关性并没有持续存在(P=0.35)。结论几种脂蛋白亚组分中甘油三酯的增加以及其他脂蛋白亚组分脂质和几种小代谢物(参与同型半胱氨酸循环、酮体形成和肌肉代谢)水平的降低可能表明存在营养不良风险。在更大的群体中进行验证后,这些指标可指导重症监护室收治的重伤患者采取预防性营养措施。
{"title":"Relevance of plasma lipoproteins and small metabolites in assessment of nutritional status among patients with severe injuries","authors":"","doi":"10.1016/j.jointm.2024.02.004","DOIUrl":"10.1016/j.jointm.2024.02.004","url":null,"abstract":"<div><h3>Background</h3><p>This study aimed to identify plasma lipoproteins and small metabolites associated with high risk of malnutrition during intensive care unit (ICU) stay in patients with severe injuries.</p></div><div><h3>Methods</h3><p>This observational prospective exploratory study was conducted at two level-1 trauma centers in the Netherlands. Adult patients (aged ≥18 years) who were admitted to the ICU for more than 48 h between July 2018 and April 2022 owing to severe injuries (polytrauma, as defined by Injury Severity Scores of ≥16) caused by blunt trauma were eligible for inclusion. Partial least squares discriminant analysis was used to analyze the relationship of 112 lipoprotein-related components and 23 small metabolites with the risk of malnutrition (modified Nutrition Risk in Critically Ill score). Malnutrition was diagnosed based on Subjective Global Assessment scores. The relationship of lipoprotein properties and small metabolite concentrations with malnutrition (during ICU admission) was evaluated using mixed effects logistic regression.</p></div><div><h3>Results</h3><p>Overall, 51 patients were included. Lower (very) low-density lipoprotein ([V]LDL) (free) cholesterol and phospholipid levels, low particle number, and higher levels of LDL triglycerides were associated with a higher risk of malnutrition (variable importance in projection [VIP] value &gt;1.5). Low levels of most (V)LDL and intermediate-density lipoprotein subfractions and high levels of high-density lipoprotein Apo-A1 were associated with the diagnosis of malnutrition (VIP value &gt;1.5). Increased levels of dimethyl sulfone, trimethylamine N-oxide, creatinine, N, N-dimethylglycine, and pyruvic acid and decreased levels of creatine, methionine, and acetoacetic acid were also indicative of malnutrition (VIP value &gt;1.5). Overall, 14 lipoproteins and 1 small metabolite were significantly associated with a high risk of malnutrition during ICU admission (<em>P</em> &lt;0.05); however, the association did not persist after correcting the false discovery rate (<em>P</em>=0.35 for all).</p></div><div><h3>Conclusion</h3><p>Increased triglyceride in several lipoprotein subfractions and decreased levels of other lipoprotein subfraction lipids and several small metabolites (involved in the homocysteine cycle, ketone body formation, and muscle metabolism) may be indicative of malnutrition risk. Following validation in larger cohorts, these indicators may guide institution of preventive nutritional measures in patients admitted to the ICU with severe injuries.</p></div>","PeriodicalId":73799,"journal":{"name":"Journal of intensive medicine","volume":"4 4","pages":"Pages 496-507"},"PeriodicalIF":0.0,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667100X24000380/pdfft?md5=b352dc663650351f572332b8c2564c95&pid=1-s2.0-S2667100X24000380-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140759253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Septic cardiomyopathy phenotype in the critically ill may depend on antimicrobial resistance 重症患者的脓毒性心肌病表型可能取决于抗菌药耐药性
Pub Date : 2024-04-08 DOI: 10.1016/j.jointm.2023.11.009
Vasiliki Tsolaki , Kyriaki Parisi , George E. Zakynthinos , Efrosini Gerovasileiou , Nikitas Karavidas , Vassileios Vazgiourakis , Epaminondas Zakynthinos , Demosthenes Makris

Background

Sepsis is a life-threatening organ dysfunction, and septic cardiomyopathy (SCM) may complicate the course of the disease. Infection with multidrug-resistant (MDR) pathogens has been linked with worse outcomes. This study aims to evaluate SCM in patients with infections caused by different antimicrobial-resistant phenotypes.

Method

This retrospective study included patients with sepsis/septic shock, hospitalized, and intubated in the intensive care unit of the University Hospital of Larissa between January 2022 and September 2023 with echocardiographic data during the first two days after infection onset. The patients were divided into two groups: non-MDR-SCM group and MDR-SCM group. The cardiac function was compared between the two groups.

Result

A total of 62 patients were included in the study. Forty-four patients comprised the MDR-SCM and 18 the non-MDR-SCM group. Twenty-six patients (41.9%) presented with left ventricular (LV) systolic dysfunction, and ≤35% right ventricular fractional area change (RVFAC) was present in 56.4%. LV systolic function was more severely impaired in the non-MDR-SCM group (left ventricular ejection fraction, 35.8% ±4.9% vs. 45.6%±2.4%, P=0.049; LV outflow tract velocity time integral, [10.1±1.4] cm vs. [15.3±0.74] cm, P=0.001; LV-Strain, –9.02%±0.9% vs. –14.02%±0.7%, P=0.001). The MDR-SCM group presented with more severe right ventricular (RV) dilatation (right ventricular end-diastolic area/left ventricular end-diastolic area, 0.81±0.03 vs. 0.7±0.05, P=0.042) and worse RV systolic function (RVFAC, 32.3%±1.9% vs. 39.6%±2.7%, P=0.035; tricuspid annular plane systolic excursion, [15.9±0.9] mm vs. [18.1±0.9] mm, P=0.165; systolic tissue Doppler velocity measured at the lateral tricuspid annulus, [9.9±0.5] cm/s vs. [13.1±0.8] cm/s, P=0.002; RV-strain, –11.1%±0.7% vs. –15.1%±0.9%, P=0.002).

Conclusion

SCM related to MDR infection presents with RV systolic dysfunction predominance, while non-MDR-SCM is mainly depicted with LV systolic dysfunction impairment.

背景败血症是一种危及生命的器官功能障碍,而败血症性心肌病(SCM)可能会使病程复杂化。耐多药(MDR)病原体感染与更差的预后有关。这项回顾性研究纳入了 2022 年 1 月至 2023 年 9 月期间在拉里萨大学医院重症监护室住院并插管的脓毒症/脓毒性休克患者,他们在感染发生后的头两天都接受了超声心动图检查。患者被分为两组:非 MDR-SCM 组和 MDR-SCM 组。研究共纳入 62 名患者。研究共纳入 62 例患者,其中 44 例为 MDR-SCM 组,18 例为非 MDR-SCM 组。26名患者(41.9%)出现左心室收缩功能障碍,56.4%的患者右心室折返面积(RVFAC)变化≤35%。非 MDR-SCM 组的左心室收缩功能受损更严重(左心室射血分数,35.8%±4.9% vs. 45.6%±2.4%,P=0.049;左心室流出道速度时间积分,[10.1±1.4] cm vs. [15.3±0.74] cm,P=0.001;左心室应变,-9.02%±0.9% vs. -14.02%±0.7%,P=0.001)。MDR-SCM 组的右心室(RV)扩张更为严重(右心室舒张末期面积/左心室舒张末期面积,0.81±0.03 vs. 0.7±0.05,P=0.042)。05,P=0.042)和更差的 RV 收缩功能(RVFAC,32.3%±1.9% vs. 39.6%±2.7%,P=0.035;三尖瓣环平面收缩期偏移,[15.9±0.9] mm vs. [18.1±0.9] mm,P=0.结论与 MDR 感染相关的 SCM 主要表现为 RV 收缩功能障碍,而非 MDR-SCM 主要表现为 LV 收缩功能障碍。
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引用次数: 0
Recombinant human thrombopoietin in alleviating endothelial cell injury in sepsis 重组人血小板生成素在减轻脓毒症内皮细胞损伤方面的作用
Pub Date : 2024-04-04 DOI: 10.1016/j.jointm.2023.12.006
Yun Xie, Hui Lv, Daonan Chen, Peijie Huang, Shaohong Wu, Hongchao Shi, Qi Zhao, Ruilan Wang

Background

To evaluate the effect of recombinant human thrombopoietin (rhTPO) on clinical prognosis by exploring changes in endothelial cell injury markers and inflammatory factors in patients with sepsis after treatment with rhTPO.

Methods

This retrospective observational study involved patients with sepsis (diagnosed according to Sepsis 3.0) admitted to Shanghai General Hospital intensive care unit from January 1, 2019 to December 31, 2022. Patients were divided into two groups (control and rhTPO) according to whether they received rhTPO. Baseline information, clinical data, prognosis, and survival status of the patients, as well as inflammatory factors and immune function indicators were collected. The main monitoring indicators were endothelial cell-specific molecule (ESM-1), human heparin-binding protein (HBP), and CD31; secondary monitoring indicators were interleukin (IL)-6, tumor necrosis factor (TNF)-α, extravascular lung water index, platelet, antithrombin III, fibrinogen, and international normalized ratio. We used intraperitoneal injection of lipopolysaccharide (LPS) to establish a mouse model of sepsis. Mice were randomly divided into four groups: normal saline, LPS, LPS + rhTPO, and LPS + rhTPO + LY294002. Plasma indicators in mice were measured by enzyme-linked immunosorbent assay.

Results

A total of 84 patients were included in the study. After 7 days of treatment, ESM-1 decreased more significantly in the rhTPO group than in the control group compared with day 1 (median=38.6 [interquartile range, IQR: 7.2 to 67.8] pg/mL vs. median=23.0 [IQR: −15.7 to 51.5] pg/mL, P=0.008). HBP and CD31 also decreased significantly in the rhTPO group compared with the control group (median=59.6 [IQR: −1.9 to 91.9] pg/mL vs. median=2.4 [IQR: −23.2 to 43.2] pg/mL; median=2.4 [IQR: 0.4 to 3.5] pg/mL vs. median=−0.6 [IQR: −2.2 to 0.8] pg/mL, P <0.001). Inflammatory markers IL-6 and TNF-α decreased more significantly in the rhTPO group than in the control group compared with day 1 (median=46.0 [IQR: 15.8 to 99.1] pg/mL vs. median=31.2 [IQR: 19.7 to 171.0] pg/mL, P <0.001; median=17.2 [IQR: 6.4 to 23.2] pg/mL vs. median=0.0 [IQR: 0.0 to 13.8] pg/mL, P=0.010). LPS + rhTPO-treated mice showed significantly lower vascular von Willebrand factor (P=0.003), vascular endothelial growth factor (P=0.002), IL-6 (P <0.001), and TNF-α (P <0.001) than mice in the LPS group. Endothelial cell damage factors vascular von Willebrand factor (P=0.012), vascular endothelial growth factor (P=0.001), IL-6 (P <0.001), and TNF-α (P=0.001) were significantly elevated by inhibiting the PI3K/Akt pathway.

Conclusion

rhTPO alleviates endothelial injury and inflammatory indices in sepsis, and may regulate septic endothelial cell

背景通过探讨脓毒症患者接受rhTPO治疗后血管内皮细胞损伤标志物和炎症因子的变化,评估重组人血小板生成素(rhTPO)对临床预后的影响。方法这项回顾性观察研究涉及2019年1月1日至2022年12月31日期间上海总医院重症监护室收治的脓毒症患者(根据脓毒症3.0标准诊断)。根据患者是否接受rhTPO治疗,将其分为两组(对照组和rhTPO组)。收集患者的基线信息、临床数据、预后和生存状况,以及炎症因子和免疫功能指标。主要监测指标为内皮细胞特异性分子(ESM-1)、人肝素结合蛋白(HBP)和CD31;次要监测指标为白细胞介素(IL)-6、肿瘤坏死因子(TNF)-α、血管外肺水指数、血小板、抗凝血酶Ⅲ、纤维蛋白原和国际标准化比值。我们采用腹腔注射脂多糖(LPS)的方法建立了败血症小鼠模型。小鼠被随机分为四组:正常生理盐水组、LPS 组、LPS + rhTPO 组和 LPS + rhTPO + LY294002 组。小鼠血浆指标通过酶联免疫吸附试验测定。治疗 7 天后,与第 1 天相比,rhTPO 组的 ESM-1 降幅比对照组更明显(中位数=38.6 [四分位距:7.2 至 67.8] pg/mL vs. 中位数=23.0 [四分位距:-15.7 至 51.5] pg/mL,P=0.008)。与对照组相比,rhTPO 组的 HBP 和 CD31 也显著下降(中位数=59.6 [IQR: -1.9 to 91.9] pg/mL vs. 中位数=2.4 [IQR: -23.2 to 43.2] pg/mL;中位数=2.4 [IQR: 0.4 to 3.5] pg/mL vs. 中位数=-0.6 [IQR: -2.2 to 0.8] pg/mL,P <0.001)。与第 1 天相比,rhTPO 组炎症指标 IL-6 和 TNF-α 的下降幅度比对照组更大(中位数=46.0 [IQR: 15.中位数=31.2 [IQR: 19.7 to 171.0] pg/mL, P <0.001;中位数=17.2 [IQR: 6.4 to 23.2] pg/mL vs. 中位数=0.0 [IQR: 0.0 to 13.8] pg/mL, P=0.010)。经 LPS + rhTPO 处理的小鼠的血管冯-威廉因子(P=0.003)、血管内皮生长因子(P=0.002)、IL-6(P <0.001)和 TNF-α (P <0.001)均明显低于 LPS 组小鼠。内皮细胞损伤因子血管冯-威廉因子(P=0.012)、血管内皮生长因子(P=0.001)、IL-6(P <0.001)和TNF-α(P=0.001)在抑制PI3K/Akt通路后显著升高。
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引用次数: 0
Effectiveness and safety of Shenfu injection in septic patients with hypoperfusion: A multi-center, open-label, randomized, controlled trial 神衰注射液对低灌注脓毒症患者的有效性和安全性:多中心、开放标签、随机对照试验
Pub Date : 2024-04-04 DOI: 10.1016/j.jointm.2024.01.007

Background

To evaluate the effectiveness and safety of the Shenfu injection (SFI) combined with standard bundle treatment in septic patients with hypoperfusion.

Method

This study was a multi-center, randomized, open-label, controlled trial conducted in four teaching hospitals in China. The septic patients with hypoperfusion and traditional Chinese medicine (TCM) syndrome with Yang-Qi deficiency were enrolled from January 2019, through September 2020. Eligible patients were randomly allocated in a 1:1 ratio to either receive 60 mL of SFI infusion per day plus standard treatment (SFI group) or standard bundle treatment alone (control group). The primary outcome was 28-day all-cause mortality. Secondary outcomes were 90-day all-cause mortality time to weaning from mechanical ventilation, time to weaning from vasopressors, time to discharge from the ICU and hospital, and laboratory results after randomization.

Results

A total of 188 patients completed the trail. This study revealed that the results of the SFI group and the control groups were not statistically significant in 28-day all-cause mortality (10.6% vs. 20.2%, respectively; P=0.106). The infusion of SFI was associated with a significant reduction in the duration of vasopressor use (median=4.0 days, interquartile range [IQR]: 2.0 days–6.0 days vs. median=5.0 days, IQR: 3.0 days–8.0 days, respectively; P=0.043). Patients in the SFI group had statistically greater reductions in plasma lactate levels compared with those in the control group at the first 12 h (median=1.1 mmol/L, IQR: 0.3–2.0 mmol/L vs. median=0.0 mmol/L, IQR: −0.2 to 0.8 mmol/L, respectively; P <0.001) and 24 h (median=1.4 mmol/L, IQR: 0.3–2.2 mmol/L vs. median=0.4 mmol/L, IQR: −0.4 to 1.6 mmol/L, respectively; P=0.001).

Conclusion

SFI plus standard therapy did not significantly decrease 28-day all-cause mortality for septic patients with hypoperfusion and TCM syndrome with Yang-Qi deficiency.

Trial registration Chinese Clinical Trial Registry Identifier: ChiCTR1800020435

背景评价神府注射液联合标准捆绑治疗对低灌注脓毒症患者的有效性和安全性。方法本研究是一项多中心、随机、开放标签、对照试验,在中国四家教学医院进行。从 2019 年 1 月至 2020 年 9 月,入组了低灌注和中医阳气虚证的脓毒症患者。符合条件的患者按1:1的比例随机分配到每天输注60毫升SFI并接受标准治疗(SFI组)或单独接受标准捆绑治疗(对照组)。主要结果是 28 天的全因死亡率。次要结果为 90 天全因死亡率、机械通气断流时间、血管加压素断流时间、从重症监护室和医院出院时间以及随机分组后的实验室结果。研究显示,SFI 组和对照组的 28 天全因死亡率(分别为 10.6% 对 20.2%;P=0.106)差异无统计学意义。输注 SFI 可显著缩短血管加压药的使用时间(中位数=4.0 天,四分位间距 [IQR]:2.0 天-6.0 天 vs. 中位数=5.0 天,四分位间距 [IQR]:3.0 天-8.0 天;P=0.043)。与对照组相比,SFI 组患者在最初 12 小时(中位数=1.1 mmol/L,IQR:0.3-2.0 mmol/L vs. 中位数=0.0 mmol/L,IQR:-0.2 至 0.8 mmol/L,分别为-0.2 至 0.8 mmol/L;P <0.001)和 24 小时(中位数=1.4 mmol/L,IQR:0.3-2.2 mmol/L vs. median=0.4 mmol/L, IQR: -0.4 to 1.6 mmol/L, respectively; P=0.001)。结论SFI加标准治疗不能显著降低脓毒症伴灌注不足和中医阳气虚证患者的28天全因死亡率:ChiCTR1800020435
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Journal of intensive medicine
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