
A New Global Definition of Acute Respiratory Distress Syndrome
文章来源:PubMed
摘要信息:Background. Since the 2012 Berlin Definition of the Acute Respiratory Distress Syndrome (ARDS), several developments have supported the need for an expansion of the definition, including the use of high flow nasal oxygen (HFNO), expanding use of pulse oximetry in place of arterial blood gases, use of ultrasound for chest imaging, and the need for applicability in resource-limited settings. Methods. A Consensus Conference of 32 critical care ARDS experts was convened, had six virtual meetings (June 2021-March 2022), and subsequently obtained input from members of several critical care societies. The goal was to develop a definition that would: (1) identify patients with the currently accepted conceptual framework for ARDS; (2) facilitate rapid ARDS diagnosis for clinical care and research; (3) be applicable in resource-limited settings; (4) be useful for testing specific therapies; and (5) be practical for communication to patients and caregivers. Results. The committee made four main recommendations: (1) Include HFNO with a minimum flow rate of 30 liters/min; (2) Use arterial oxygen tension (PaO2)/FiO2 300 mmHg or SpO2/FiO2 < 315 (if SpO2 97%) to identify hypoxemia; (3) Retain bilateral opacities for imaging criteria but add ultrasound as an imaging modality, especially in resource-limited areas; and (4) In resource-limited settings, do not require PEEP, oxygen flow rate, or specific respiratory support devices. Conclusions. We propose a New Global Definition of ARDS that builds on the Berlin Definition. The recommendations also identify areas for future research, including the need for prospective assessments of feasibility, reliability, and prognostic validity of the proposed Global Definition.

The Protective Effects of Sivelestat Sodium on the Basis of Corticosteroid Therapy in Patients With Moderate-to-Severe Acute Respiratory Distress Syndrome
文章来源:PubMed
摘要信息:Objective:We aimed to evaluate the protective effects of sivelestat sodium on the basis of corticosteroid therapy in patients with moderate-to-severe acute respiratory distress syndrome (ARDS).Methods:We retrospectively investigated 127 patients with confirmed moderate-to-severe ARDS treated in the intensive care unit (ICU) at Dazhou Central Hospital. Patients were divided into the control group (corticosteroids alone) and the combination therapy of steroids and sivelestat sodium (CTSSS) group according to the therapeutic interventions. The primary outcome was in-hospital mortality. And the baseline characteristics and laboratory findings of patients were collected for analysis.Results:The overall mortality rate in 127 patients was 48.8%. There was no statistically significant difference in in-hospital mortality between the CTSSS group and the control group (45.3% vs. 56.1%). In the subgroup of patients aged < 80 years or with an Acute Physiology and Chronic Health Evaluation (APACHE) II score < 30, CTSSS could reduce the risk of mortality (odds ratio [OR] = 0.41, 95% confidence interval [CI], 0.17-0.96, p=0.041; OR = 0.31, 95% CI, 0.13-0.77, p=0.012; respectively). Among patients aged 80 years or older, those with CTSSS exhibited a significantly elevated risk of mortality (OR = 13; 95% CI, 1.20-140.73; p=0.035).Conclusion:Compared with corticosteroids alone, CTSSS could improve oxygenation index, increase lymphocyte count, protect extrapulmonary organs and reduce in-hospital mortality rate in patients with moderate-to-severe ARDS in specific subgroups (age < 80 years or APACHE II score < 30). It might be advisable to avoid CTSSS in moderate-to-severe ARDS patients aged 80 years or older. Prospective studies involving larger sample sizes are needed to verify these findings.

Population pharmacokinetics of sivelestat in Chinese patients with severe pneumonia(在中国重症肺炎患者中的群体药代动力学)
文章来源:PubMed
摘要信息:背景:缺血再灌注损伤(IRI)常导致肾脏损害。虽然中性粒细胞胞外陷阱(NETs)的存在一直被观察到,但它们对IRI的具体影响尚未确定。西维来司他钠是中性粒细胞弹性酶的抑制剂,对NET的形成至关重要,可能为肾脏IRI提供治疗方法,值得进一步研究。 方法:建立小鼠早期肾IRI模型,经损伤标志物和组织学检查证实。免疫荧光和Western blot证实NETs在肾I/R中的作用。通过一套全面的方法进一步评估肾功能和病理,包括周期性酸希夫染色(PAS)和末端脱氧核苷酸转移酶dUTP Nick末端标记(TUNEL)染色,酶联免疫吸附试验(ELISA),实时肾小球滤过率(RT-GFR)监测,聚合酶链反应(PCR),生化分析,以及额外的Western blot和免疫荧光试验。 结果:我们首先量化了肾IRI小鼠的NET表达,并在24小时达到峰值。随后,给予西维来司他钠治疗,导致MPO、CitH3降低,并减轻了肾小管损伤。此外,它还导致血清肌酐、血尿素氮(BUN)、中性粒细胞明胶酶相关脂钙蛋白(NGAL)和肾损伤分子-1 (KIM-1)水平降低。降低肾组织炎症标志物白介素-6 (IL-6)和肿瘤坏死因子-α (TNF-α)的丰度,减轻氧化应激指标丙二醛(MDA)和4羟基烯醛(4HNE)的水平,并伴有肾I/R小鼠肾细胞凋亡减少和GFR升高。 结论:西维来司他钠通过下调中性粒细胞NETs,减少炎症、氧化应激和细胞凋亡,从而改善肾IRI,从而增强肾功能。

Neutrophil Extracellular Traps Drive Kidney Stone Formation(中性粒细胞胞外陷阱驱动肾结石形成)
文章来源:PubMed
摘要信息:本研究旨在探讨中性粒细胞胞外陷阱 (NETs) 对肾结石的贡献。方法:来自GSE73680和生物信息学分析的微阵列数据用于鉴定肾结石患者的差异表达基因。通过乙二醇和氯化铵给药建立肾结石大鼠模型。采集血浆检测cf-DNA、DNase I、MPO-DNA、H3Cit、NE,生化分析检测超氧化物歧化酶、丙二醛、肌酐、血尿素氮、钙。免疫荧光染色检测肾组织中 MPO 、 H3Cit 和 NE 。通过 TUNEL 测定评估细胞凋亡。应用 HE 、 过碘酸-Schiff 和 Von Kossa 染色来确定肾脏中的组织学结构、钙沉积和结石形成。给予中性粒细胞弹性蛋白酶抑制剂 Sivelestat (SIVE) 抑制大鼠 NET。结果:在具有 Randall 斑块的肾组织和正常组织中共鉴定出 403 个差异表达基因,其中 270 个上调和 133 个下调基因。对这些失调的基因进行基因本体富集、KEGG 通路和蛋白质-蛋白质相互作用网络分析。此外,在肾结石患者中观察到 NET 标志物增加,包括 cf-DNA 、 DNase I、MPO-DNA 、 H3Cit 和 NE 以及钙沉积物。随后,我们建立了肾结石大鼠模型。我们发现肾结石大鼠 NET 形成显著升高,随着肾结石的发展,肾小管损伤和凋亡细胞增强。引人注目的是,我们发现通过 SIVE 抑制 NETs 可以显着减少钙沉积和凋亡细胞,减轻肾小管损伤,从而改善肾功能。结论:NETs 会促进肾结石的形成,从而加重肾损伤。我们的研究将 NETs 确定为肾结石的潜在诊断和治疗生物标志物。

Ten-year retrospective analysis of multiple trauma complicated by pulmonary contusion
摘要信息:Background:This study reports a 10-year retrospective analysis of multiple trauma complicated by pulmonary contusion. The purpose of this study is to ascertain the risk factors for mortality due to trauma in patients with pulmonary contusion, the impact of various treatment options for prognosis, and the risk factors for concurrent Acute Respiratory Distress Syndrome (ARDS). Methods:We retrospectively analyzed 252 trauma patients with lung contusion admitted to the General Hospital of Guangzhou Command from January 2000 to June 2011 by using the statistical processing system SPSS 17.0 for Windows. Results:We included 252 patients in our study, including 214 males and 38 females. The average age was 37.1 ± 14.9 years. There were 110 cases admitted to the ICU, of which 26 cases with ARDS. Nine of the 252 patients died. We compared those who survived with those who died by gender and age, the difference was not statistically significant (P = 0.199, P = 0.200). Separate univariate analysis of those who died and those who survived found that shock on admission (P = 0.000), coagulation disorders (P = 0.000), gastrointestinal bleeding (P = 0.02), the need for emergency surgery on admission (P = 0.000), pre-hospital intubation (P = 0.000), blood transfusion within 24 hours (P = 0.006), the use of mechanical ventilation (P = 0.000), and concurrent ARDS (P = 0.000) are poor prognosis risk factors. Further logistic analysis, including the admission GCS score (OR = 0.708, 95% CI 0.516-0.971, P = 0.032), ISS score (OR 1.135, 95% CI 1.006-1.280, P = 0.039), and concurrent ARDS (OR = 15.814, 95% CI 1.819-137.480, P = 0.012), identified the GCS score, ISS score and concurrent ARDS as independent risk factors of poor prognosis. Shock (OR = 9.121, 95% CI 0.857-97.060, P = 0.067) was also related to poor prognosis. Patients with injury factors such as road accident, falling injury, blunt injury and crush injury, et al.(P = 0.039), infection (P = 0.005), shock (P = 0.004), coagulation disorders (P = 0.006), emergency surgery (P = 0.01), pre-hospital intubation (P = 0.000), chest tube insertion (P = 0.004), blood transfusion (P = 0.000), usage of hormones (P = 0.002), phlegm (P = 0.000), ventilation (P = 0.000) were at a significantly increased risk for ARDS complications. Conclusions:Those patients with multiple trauma and pulmonary contusion admitted to the hospital with shock, coagulopathy, a need for emergency surgery, pre-hospital intubation, and a need for mechanical ventilation could have a significantly increased risk of mortality and ARDS incidence. A risk for poor prognosis was associated with gastrointestinal bleeding. A high ISS score, high APACHE2, and low GCS score were independent risk factors for poor prognosis. If patients developed an infection or were given drainage, hormones, and phlegm treatment, they were at higher risk of ARDS. Pre-hospital intubation and drainage were independent risk factors for ARDS. In patients with ARDS, the ICU stay, total length of stay, and hospital costs might increase significantly. A GCS score < 5.5, APACHE 2 score > 16.5, and ISS score > 20.5 could be considered indicators of poor prognosis for patients with multiple trauma and lung contusion.

Sivelestat sodium for aspiration-related acute lung injury: a review and analysis of published case reports
摘要信息:Background:There are conflicting views on the of sivelestat sodium (sivelestat-Na) on acute lung injury. Methods:The efficacy of sivelestat-Na on aspiration-related acute lung injury was analyzed by reviewing case reports published before or after the appearance of the drug on the clinical practice in Japan. Data were analyzed from the 23 sivelestat-treated cases and 5 non-sivelestat cases. Results:Sivelestat-Na was administered by 0.2 mg x kg(-1) x hr(-1) for 10 +/- 4 (mean +/- SD) days. PaO2/ ratio increased significantly from 124 +/- 59 mmHg of baseline to 253 +/- 79 mmHg on the third and to 361 +/- 84 mmHg on the termination of the therapy. Significantly better response was observed if the drug was administered within 24 hours after aspiration for patients with background of neurological disease, in which the increases in the P/F ratio were greater and the duration of the drug administration was shorter compared with other patients. In comparison with the non-sivelestat cases, sivelestat-Na therapy appears to be associated with shorter ventilator days or higher P/F increase, although sivelestat-Na costs higher. Conclusions:These results suggest the possibility of conducting prospective clinical trials to assess the efficacy of early sivelestat-Na therapy for aspiration-related acute lung injury.