摘要信息：Sivelestat sodium hydrate (Ono Pharmaceutical Co., Osaka, Japan) is a selective inhibitor of neutrophil elastase (NE) and is effective in reducing acute lung injury associated with systemic inflammatory response syndrome (SIRS). We conducted a prospective randomized controlled study to investigate the efficacy of perioperative administration of sivelestat sodium hydrate to prevent postoperative acute lung injury in patients undergoing thoracoscopic esophagectomy and radical lymphadenectomy. Twenty-two patients with thoracic esophageal cancer underwent video-assisted thoracoscopic esophagectomy with extended lymph node dissection in our institution between April 2007 and November 2008. Using a double-blinded method, these patients were randomly assigned to one of two groups preoperatively. The active treatment group received sivelestat sodium hydrate intravenously for 72 hours starting at the beginning of surgery (sivelestat-treated group; n= 11), while the other group received saline (control group; n= 11). All patients were given methylprednisolone immediately before surgery. Postoperative clinical course was compared between the two groups. Two patients (one in each group) were discontinued from the study during the postoperative period because of surgery-related complications. Of the remaining 20 patients, 2 patients who developed pneumonia within a week after surgery were excluded from some laboratory analyses, so data from 18 patients (9 patients in each group) were analyzed based on the arterial oxygen pressure/fraction of inspired oxygen ratio, white blood cell count, serum C-reactive protein level, plasma cytokine levels, plasma NE level, and markers of alveolar type II epithelial cells. In the current study, the incidence of postoperative morbidity did not differ between the two groups. The median duration of SIRS in the sivelestat-treated group was significantly shorter than that in the control group: 17 (range 9-36) hours versus 49 (15-60) hours, respectively (P= 0.009). Concerning the parameters used for the diagnosis of SIRS, the median heart rates on postoperative day (POD) 2 were significantly lower in the sivelestat-treated group than in the control group (P= 0.007). The median arterial oxygen pressure/fraction of inspired oxygen ratio of the sivelestat-treated group were significantly higher than those of the control group on POD 1 and POD 7 (POD 1: 372.0 [range 284.0-475.0] vs 322.5 [243.5-380.0], respectively, P= 0.040; POD 7: 377.2 [339.5-430.0] vs 357.6 [240.0-392.8], P= 0.031). Postoperative white blood cell counts, serum C-reactive protein levels, plasma interleukin-1beta, tumor necrosis factor-alpha levels, and plasma NE levels did not differ significantly between the two groups at any point during the postoperative course, nor did serum Krebs von den Lungen 6, surfactant protein-A, or surfactant protein-D levels, which were used as markers of alveolar type II epithelial cells to evaluate the severity of lung injury. Plasma interleukin-8 levels were significantly lower in the sivelestat-treated group than in the control group on POD 3 (P= 0.040). In conclusion, perioperative administration of sivelestat sodium hydrate (starting at the beginning of surgery) mitigated postoperative hypoxia, partially suppressed postoperative hypercytokinemia, shortened the duration of SIRS, and stabilized postoperative circulatory status after thoracoscopic esophagectomy.

摘要信息：Purpose:The goal of this retrospective study was to evaluate the effects of perioperative administration of sivelestat sodium hydrate, a selective neutrophil elastase inhibitor, on the clinical course after radical surgery for esophageal cancer. Methods:The effects of sivelestat on postoperative systemic inflammatory reactions and respiratory function were examined in 53 patients who underwent radical surgery for esophageal cancer between April 2004 and March 2005 with (n = 26, sivelestat group) and without (n = 27, control group) the administration of sivelestat. Results:The average age in the sivelestat group was higher than that in the control group, but there were no other differences in the background factors between the two groups. The postoperative oxygenation (PaO(2)/FiO(2) ratio) did not differ between the groups, but the decrease in oxygen saturation (SpO(2)) was significantly inhibited in the sivelestat group compared with the control group (p < 0.01). A significant inhibition of the increase in the CRP level also occurred in the sivelestat group (p < 0.01). The patients in the sivelestat group were also hospitalized for shorter periods compared to those in the control group. Conclusion:The early administration of sivelestat to patients receiving radical surgery for esophageal cancer can inhibit postoperative systemic inflammatory reactions and it might also have a beneficial effect on the prognosis.

摘要信息：Background:This study was undertaken to assess the value of administering perioperative sivelestat sodium hydrate (SSH), a selective neutrophil elastase inhibitor, after video-assisted thoracoscopic oesophagectomy for cancer. Method:Thirty-one consecutive patients with thoracic oesophageal cancer selected to undergo video-assisted thoracoscopic oesophagectomy with lymph node dissection between March 2007 and March 2009 were assigned randomly to a treatment group that received SSH intravenously for 7 days from the beginning of surgery (16 patients) and a control group that received saline (15). The primary endpoint was pulmonary function based on the arterial partial pressure of oxygen/fraction of inspired oxygen ratio (P/F ratio) during the first 9 days after surgery. Secondary endpoints included platelet count, serum C-reactive protein (CRP) concentration, plasma neutrophil elastase-α(1)-antitrypsin complex level, duration of mechanical ventilation and systemic inflammatory response syndrome (SIRS), and length of intensive care unit (ICU) and hospital stay. Results:The mean P/F ratio of patients who received SSH was significantly higher than that of the control group on postoperative days 1-5 and 7. Duration of mechanical ventilation and SIRS, and length of ICU stay were significantly shorter in the treatment group. Serum CRP concentration on postoperative day 9 was significantly lower (P = 0·048), platelet counts on days 2, 3 and 5 were higher (P = 0·012, P = 0·049 and P = 0·006 respectively), and the incidence of postoperative acute lung injury was significantly lower following SSH treatment (P = 0·023). Conclusion:Perioperative sivelestat may maintain postoperative pulmonary function following video-assisted oesophagectomy.

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。