摘要信息：Gastric aspiration is the major cause of acute lung injury (ALI) and acute respiratory distress syndrome. Aspiration-induced ALI is believed to be, at least in part, facilitated by neutrophil-derived mediators and toxic molecules. We conducted a prospective cohort study based on the hypothesis that sivelestat, a specific neutrophil elastase inhibitor, is effective for treating ALI following gastric aspiration. Forty-four ALI patients who showed evidence of aspiration were observed within 12 h before intensive care unit admission and who had been mechanically ventilated within 12 h after admission were included in this study. Lung injury score (LIS) and PAO2/FiO2 (P/F) ratio on day 7 were defined as the primary outcomes of the study. Twenty-three patients were assigned to the sivelestat group and 21 to the control group. In univariate analyses, the proportions of patients with LIS lower than 1.0 on day 7 and a P/F greater than 300 on day 7 were significantly higher in the sivelestat group than in the control group (60.9% vs. 26.3%, P = 0.03; 87.0% vs. 36.8%, P = 0.001). In the logistic regression model, the use of sivelestat was an independent predictor for LIS lower than 1.0 on day 7 (relative risk, 7.4; 95% confidence interval [CI], 1.51-36.48) and for a P/F ratio higher than 300 on day 7 (relative risk, 18.5; 95% CI, 2.72-126.46). In the Cox proportional hazards model, the use of sivelestat was associated with a lower cumulative proportion of patients who received mechanical ventilation during the initial 14 days (hazard ratio, 2.6; 95% CI, 1.17-5.55).

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.

摘要信息：Background: We aimed to assess the efficacy of the neutrophil elastase inhibitor, sivelestat, in the treatment of sepsis-induced acute respiratory distress syndrome (ARDS) and septic cardiomyopathy (SCM). Methods: Between January 2019 and December 2021, we conducted a randomized trial on patients who had been diagnosed with sepsis-induced acute respiratory distress syndrome (ARDS) and septic cardiomyopathy (SCM) at Wuhan Union Hospital. The patients were divided into two groups by random envelop method, the Sivelestat group and the Control group. We measured the serum concentrations of Interleukin (IL)-6, IL-8, Tumor necrosis factor-α (TNF-α), and High-mobility group box 1 (HMGB1) at five time points, which were the baseline, 12 h, 24 h, 48 h, and 72 h after admission to the ICU. We evaluated the cardiac function by sonography and the heart rate variability (HRV) with 24-hour Holter recording between the time of admission to the intensive care unit (ICU) and 72 h after Sivelestat treatment. Results: From January 2019 to December 2021, a total of 70 patients were included in this study. The levels of IL-6, IL-8, and TNF-α were significantly lower in the Sivelestat group at different time points (12 h, 24 h, 48 h, and 72 h). HMGB1 levels were significantly lower at 72 h after Sivelestat treatment (19.46 ± 2.63pg/mL vs. 21.20 ± 2.03pg/mL, P = 0.003). The stroke volume (SV), tricuspid annular plane systolic excursion (TAPSE), early to late diastolic transmitral flow velocity (E/A), early (e') and late (a') diastoles were significantly low in the Control group compared with the Sivelestat group. Tei index was high in the Control group compared with the Sivelestat group (0.60 ± 0.08 vs. 0.56 ± 0.07, P = 0.029). The result of HRV showed significant differences in standard deviation of normal-to-normal intervals (SDNN), low frequency (LF), and LF/HF (high frequency) between the two groups. Conclusions: Sivelestat can significantly reduce the levels of serum inflammatory factors, improve cardiac function, and reduce heart rate variability in patients with Sepsis-induced ARDS and SCM.

摘要信息：目的 观察西维来司他钠联合乌司他丁治疗脓毒症所致急性呼吸窘迫综合征(ARDS)的临床疗效。方法 选取2020年1月至2023年5月本院收治的104例脓毒症所致ARDS患者,经计算机随机数字生成器分为对照组(常规治疗+西维来司他钠)、联合组(常规治疗+西维来司他钠+乌司他丁),各52例。比较治疗前后两组Murray肺损伤评分(MLIS)评分、序贯器官功能衰竭(SOFA)评分、血管外肺水指数(ELWI)、动脉血氧分压/吸氧浓度分数(Pa0,i0,)、白细胞计数(WBC)、中性粒细胞百分比(NEUT%)内皮细胞特异性分子(ESM-1)、可溶性尿激酶型纤溶酶原激活物受体(suPAR)及白细胞介素-6(ⅡL-6)水平:比较两组恢复速度、预后情况及不良反应。结果 对照组、联合组治疗前MLIS评分、SOFA评分ELII、PaO.F;O,、WBC、NEUT%、ESM-1、SUPAR及I-6水平比较,差异无统计学意义(P>0.05)。治疗后联合组MLIS评分、SOFA评分、ELWI、WBC、NEUT%、ESM-1、suPAR及I6水平均低于对照组(P<0.05)Pa0,/Fi0,高于对照组(P<0.05);联合组机械通气时间、ICU住院时间均短于对照组(P<0.05).28 d病死率低于对照组(P<0.05)。两组治疗期间均未发生严重不良反应。结论 西维来司他钠联合乌司他丁应用于脓毒症所致ARDS 中可减轻患者肺损伤及炎症反应,加快恢复,改善肺功能及预后,且安全性高。

摘要信息：To investigate the effects of neutrophil elastase inhibitor (sivelestat sodium) on gastrointestinal function in sepsis. A reanalysis of the data from previous clinical trials conducted at our center was performed. Septic patients were divided into either the sivelestat group or the non-sivelestat group. The gastrointestinal dysfunction score (GIDS), feeding intolerance (FI) incidence, serum levels of intestinal barrier function and inflammatory biomarkers were recorded. The clinical severity and outcome variables were also documented. A total of 163 septic patients were included. The proportion of patients with GIDS ≥2 in the sivelestat group was reduced relative to that in the non-sivelestat group (9.6% vs. 22.5%, p = 0.047) on the 7th day of intensive care unit (ICU) admission. The FI incidence was also remarkably reduced in the sivelestat group in contrast to that in the non-sivelestat group (21.2% vs. 37.8%, p = 0.034). Furthermore, the sivelestat group had fewer days of FI [4 (3, 4) vs. 5 (4-6), p = 0.008]. The serum levels of d-lactate (p = 0.033), intestinal fatty acid-binding protein (p = 0.005), interleukin-6 (p = 0.001), white blood cells (p = 0.007), C-reactive protein (p = 0.001), and procalcitonin (p < 0.001) of the sivelestat group were lower than those of the non-sivelestat group. The sivelestat group also demonstrated longer ICU-free days [18 (0-22) vs. 13 (0-17), p = 0.004] and ventilator-free days [22 (1-24) vs. 16 (1-19), p = 0.002] compared with the non-sivelestat group. In conclusion, sivelestat sodium administration appears to improve gastrointestinal dysfunction, mitigate dysregulated inflammation, and reduce disease severity in septic patients.

摘要信息：Background: Sepsis is a leading cause of preventable death around the world. Population-based estimation of sepsis incidence is lacking in China. In this study, we aimed to estimate the population-based incidence and geographic variation of hospitalized sepsis in China. Methods: We retrospectively identified hospitalized sepsis from the nationwide National Data Center for Medical Service (NDCMS) and the National Mortality Surveillance System (NMSS) by ICD-10 codes for the period from 2017 to 2019. In-hospital sepsis case fatality and mortality rate were calculated to extrapolate the national incidence of hospitalized sepsis. The geographic distribution of hospitalized sepsis incidence was examined using Global Moran's Index. Results: We identified 9,455,279 patients with 10,682,625 implicit-coded sepsis admissions in NDCMS and 806,728 sepsis-related deaths in NMSS. We estimated that the annual standardized incidence of hospitalized sepsis was 328.25 (95% CI 315.41-341.09), 359.26 (95% CI 345.4-373.12) and 421.85 (95% CI 406.65-437.05) cases per 100,000 in 2017, 2018 and 2019, respectively. We observed 8.7% of the incidences occurred among neonates less than 1 year old, 11.7% among children aged 1-9 years, and 57.5% among elderly older than 65 years. Significant spatial autocorrelation for incidence of hospitalized sepsis was observed across China (Moran's Index 0.42, p = 0.001; 0.45, p = 0.001; 0.26, p = 0.011 for 2017, 2018, 2019, respectively). Higher number of hospital bed supply and higher disposable income per capita were significantly associated with a higher incidence of hospitalized sepsis. Conclusion: Our study showed a greater burden of sepsis hospitalizations than previous estimated. The geographical disparities suggested more efforts were needed in prevention of sepsis.

摘要信息：【摘要】 目的 探讨西维来司他钠治疗伴有急性呼吸窘迫综合征(ARDS)的脓毒症患者的效果。方法 选择河南科技大学第一附属医院 2021 年3 月至2022 年12 月收治的88 例伴有 ARDS 的脓毒症患者作为研究对象,采用双色球法分为对照组与观察组,每组44 例,对照组采用常规治疗,观祭组采用常规治疗联合西维来司他钠,比较两组炎症因子、肺损伤评分、序贯器官衰竭评分、急性生理与慢性健康评分(APACHE-I)、血小板计数(PLT)、氧合指数、机械通气时间与 14d病死率。结果 治疗前,两组炎症因子、PLT、氧合指数、肺损伤评分、序贯器官衰竭评分、APACHE-I评分比较,差异未见统计学意义(P>0.05);治疗后,观察组炎症因子、肺损伤评分、序贯器官衰竭评分、APACHE-Ⅱ评分低于对照组,PLT、氧合指数高于对照组,差异有统计学意义(P<0.05):观察组机械通气时间短于对照组,差异有统计学意义(P<0.05),但两组病死率比较,差异未见统计学意义(P>0.05)。结论 西维来司他钠用于伴有 ARDS 的脓毒症患者的治疗中,与常规治疗方案比较,可更好地改善肺损伤,避免器官衰竭,提升患者的健康状况,同时还能更好地减轻炎症反应,缩短机械通气时间。

摘要信息：脓毒性休克治疗过程中容易并发急性呼吸窘迫综合症(acute respiratory distress syndrome，ARDS)，一旦出现 ARDS，患者往往预后不佳，西维 来司他钠是全球唯一获批适应证为ARDS治疗的药物。本次研究报道1 例西维来司他钠治疗泌尿系脓毒性休克并发ARDS。

摘要信息：【摘要】 目的 探讨西维来司他钠治疗脓毒症伴急性呼吸窘迫综合征(ARDS)的疗效。方法 120 例脓毒症伴 ARDS 患者随机分为3组.C组给予常规对症治疗,U组和S组在此基础上分别给予鸟司他丁和西维来司他钠治疗。比较各组治疗7天后的炎症指标、氧合指数(Pa0,/Fi0,)、血小板计数(PLT)、Munay 肺损伤评分(MLIS)、序贯器官衰竭评分(SOFA)、机械通气时间(VT)和14天病死率。结果 治疗后U组和S组各观察指标均优于C组。S组PaO,/Fi0,、PIT高于U组,MLIS评分、VT低于U组(P<0.05),两组炎症指标、SOFA 评分和 14 天病死率无显著差异(P>0.05)。Pa0,/Fi0,与 PIT呈显著正相关(r=0.893,P<0.05),MLIS 评分与 Pa0,/F0,呈显著负相关(r=-0.874.P<0.05)。结论 早期应用西维来司他钠可显著减轻脓毒症伴 ARDS 患者的炎症反应,提高 PaO,/Fi0,和 PLT 计数,缩短 VT 和降低14天病死率。

摘要信息：Background: Acute respiratory distress syndrome (ARDS) is one of the most organ dysfunctions in sepsis. Although the development of therapeutic strategies such as protective mechanical ventilation technology has improved the mortality of ARDS patients, there is currently no effective drug for reducing the associated mortality. Our study aims to investigate the efficacy, safety, and pharmacoeconomics of sivelestat sodium in patients with septic ARDS, for providing the basis on clinical use of this drug. Methods: This was a retrospective study of 140 patients with septic ARDS. Clinical information including general conditions, mechanical ventilation time, drug cost parameters, and adverse reactions. The partial pressure of O2/fraction of inspired oxygen (PaO2/FiO2), acute physiology and chronic health evaluation score (APACHE II score) and sequential organ failure assessment (SOFA score) are for assessing the severity illness. To evaluate the efficacy of sivelestat sodium on septic ARDS patients by comparing length of mechanical ventilation and intensive care unit (ICU) hospitalization, cost of hospitalization and mortality between the two groups. Results: There were no significant differences in the incidence of organ failure, biochemical data, blood gas analysis, acute physiology and chronic health evaluation (APACHE II score), and SOFA score between the two groups on the day of admission. The PaO2/FiO2, APACHE II score, and SOFA score of the sivelestat sodium group were significantly better than in the control group (P<0.05). The length of mechanical ventilation, length of ICU hospitalization, and cost of ICU hospitalization were all lower in the sivelestat sodium group (P<0.05). No adverse events were reported during the study period. Conclusions: Sivelestat sodium significantly improves the oxygenation in patients with septic ARDS, together with reducing mechanical ventilation, ICU hospitalization, and medical costs.