Effect of ulinastatin combined with thymosin alpha1 on sepsis: A systematic review and meta-analysis of Chinese and Indian patients

Liu, Dadong; Yu, Zongying; Yin, Jie; Chen, Yikun; Zhang, Hao; Fan, Xiaoxuan; Fu, Haiyan; Wan, Bing

doi:10.1016/j.jcrc.2016.12.013

Cited by 33 publications

(24 citation statements)

References 40 publications

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“…In other studies, although they found significantly reduced mortality rate by the use of ulinastatin, the length of stay in the hospital was not significantly prolonged 22 , 29 . In a systematic review and meta-analysis, treatment with ulinastatin was not able to reduce the duration of vasopressor use and length of stay in ICU 12 . However, the length of stay in ICU and hospital can be influenced by many factors such as the criteria for ICU discharge, financial insurance of a patient, economic status and culture believes.…”

Section: Discussionmentioning

confidence: 94%

“…Third, other agents that have inflammatory modulatory effects were not included for analysis in the present study, making the presence of potential uncontrolled confounding possible. There have been evidence that ulinastain, when combined with other agents such as Xuebijing and thymosin alpha1, can have better effect than used alone 12 , 37 . These agents were seldom used in our hospital, and thus cannot be analyzed in the present study.…”

Section: Discussionmentioning

confidence: 99%

“…However, clinical studies are conflicting. While some studies showed benefits of ulinastatin 11 , 12 , others failed to replicate the results 13 . A recent systematic review showed no statistical difference on mortality between ulinastatin and control groups 11 .…”

Section: Introductionmentioning

confidence: 99%

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Ulinastatin is effective in reducing mortality for critically ill patients with sepsis: a causal mediation analysis

Yan

Chen

2018

Sci Rep

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Ulinastatin has been found to have anti-inflammatory effect for patients with sepsis. However, its clinical effects were conflicting. The study aimed to investigate the cost-effectiveness of ulinastatin and to perform mediation analysis to explore the proportion of the total effects that can be explained by inflammatory responses. This is a retrospective study involving critically ill patients with sepsis from January 2014 to July 2017. A total of 263 patients were included in the study, involving 179 patients in the ulinastatin group and 84 in the control group. Ulinastatin group showed significantly lower 28-day mortality rate than that in the control group (31% vs. 55%; p < 0.001). Both total (46330 [26000,83500] vs. 19870 [8747,41140] RMB; p < 0.01) and drug cost (18210 [9492,31920] vs. 7230 [2675,19270] RMB; p < 0.01) were significantly higher in the ulinastatin group than the control group. In multivariable model, the adjusted odds ratio for ulinastatin was 0.304 (95% CI: 0.152 to 0.592; p = 0.001). The mediation analysis showed that the use of ulinastatin was able to reduce the probability of death by 23.5%. The average causal mediation effect of delta C-reactive protein (CRP) was 8%, accounting for 35% of the total effect.

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Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

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Ulinastatin is effective in reducing mortality for critically ill patients with sepsis: a causal mediation analysis

Yan

Chen

2018

Sci Rep

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“…Tα1, a biological response modifier, could enhance the immune system through promoting differentiation and maturation of T lymphocytes. 48 , 49 Wnt4 has been proven to be required for the development of the thymus, as it controls mesenchymal-to-epithelial transition and epithelial cell proliferation in the thymus. 50 β-actin, an important cytoskeletal protein, seems to be overexpressed in actively moving cancer cells.…”

Section: Discussionmentioning

confidence: 99%

A novel mechanism of tumor-induced thymic atrophy in mice bearing H22 hepatocellular carcinoma

Sun

Feng

et al. 2018

CMAR

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BackgroundThymic atrophy was discovered in tumor-bearing mice in recent years.MethodsFlow cytometry was carried out including Annexin V-FITC/PI double staining, PI staining, Terminal dUTP nick-end labeling, CD3-FITC/CD19-PE and CD8-FITC/CD4-PE double staining. Enzyme-linked immunosorbent assay and polymerase chain reaction were also investigated.ResultsAccording to our experiments, we demonstrated that no signs of apoptosis in thymocytes were found in H22-bearing mice, while the proportions of CD4+ T cells and CD8+ T cells in thymuses were remarkably increased, the opposite tendency was found in peripheral bloods, and only CD3+CD8+ T cells were discovered in H22 solid tumors. We further discovered that the level of thymosin alpha 1 (Tα1) and the expression of Wnt4 in thymus of H22-bearing mice were significantly improved than control, which indicated the active proliferation and differentiation of thymocytes. Our study revealed that CD8+ T cells could not effectively eliminate H22 cells independently when CD4+ T cells were suppressed by tumors, while the body would only enhance the differentiation and maturation of T cells in thymuses and release them to solid tumor to reinforce antitumor immunocompetence, leading to a vicious cycle which finally led to thymic atrophy.ConclusionOur data propose a novel mechanism of tumor-induced thymic atrophy regulated by abnormal immunoreaction and may provide new ideas for the immunotherapy of tumors.

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“…Some pilot studies showed a trend towards decreasing mortality and duration of hospitalization with ulinastatin in severe sepsis [ 19 , 20 ]. A recent meta-analysis reported that compared with a control group, ulinastatin treatment could significantly decrease the 28-day mortality rate (26.9% (152/565) vs 41.6% (228/547), RR 0.64; 95% CI 0.54–0.75; P < 0.01); however, two out of eight enrolled trials were of low quality and some of them were combined with thymosin [ 21 ]. This meta-analysis included a recently published prospective, double-blind, multi-center randomized controlled trial (RCT) conducted in seven hospitals in India.…”

Section: Introductionmentioning

confidence: 99%

ADJunctive Ulinastatin in Sepsis Treatment in China (ADJUST study): study protocol for a randomized controlled trial

Jiang

Sun

et al. 2018

Trials

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BackgroundSepsis is a major challenge in critical care and is associated with high mortality. Current management of sepsis and septic shock remains mainly supportive. Both basic and clinical research has shown that ulinastatin can improve the prognosis of sepsis. The aim of this trial is to evaluate the efficacy and safety profiles of ulinastatin compared with placebo.Methods/designIn this multi-center, double-blind, randomized placebo-controlled trial we are recruiting a total of 348 subjects meeting “The Third International Consensus Definitions for Sepsis and Septic Shock” (Sepsis-3). Subjects will be randomized (1:1) to receive ulinastatin 400,000 IU three times a day for 10 days or matching placebo and usual care simultaneously. The primary outcome is 28-day all-cause mortality. Adverse events and serious adverse events will be monitored closely.DiscussionADJUST is a large, multi-center, double-blind, randomized, parallel-group, placebo-controlled trial of ulinastatin in mainland China and is well-designed on the basis of previous studies. The results of this trial may help to provide evidence-based recommendations for treatment of sepsis.Trial registrationClinicalTrials.gov, ID: NCT02647554. First registered on 27 December 2015, and last verified in December of 2016.Protocol version: 2.1, verified on 19 July 2016.

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Effect of ulinastatin combined with thymosin alpha1 on sepsis: A systematic review and meta-analysis of Chinese and Indian patients

Cited by 33 publications

References 40 publications

Ulinastatin is effective in reducing mortality for critically ill patients with sepsis: a causal mediation analysis

Ulinastatin is effective in reducing mortality for critically ill patients with sepsis: a causal mediation analysis

A novel mechanism of tumor-induced thymic atrophy in mice bearing H22 hepatocellular carcinoma

ADJunctive Ulinastatin in Sepsis Treatment in China (ADJUST study): study protocol for a randomized controlled trial

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